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Background: We evaluated associations between antepartum weight change and adverse pregnancy outcomes and between antiretroviral therapy (ART) regimens and week 50 postpartum body mass index in IMPAACT 2010., Methods: Women with human immunodeficiency virus (HIV)-1 in 9 countries were randomized 1:1:1 at 14-28 weeks' gestational age (GA) to start dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) versus DTG + FTC/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF. Insufficient antepartum weight gain was defined using Institute of Medicine guidelines. Cox-proportional hazards regression models were used to evaluate the association between antepartum weight change and adverse pregnancy outcomes: stillbirth (≥20 weeks' GA), preterm delivery (<37 weeks' GA), small size for GA (<10th percentile), and a composite of these endpoints., Results: A total of 643 participants were randomized: 217 to the DTG + FTC/TAF, 215 to the DTG + FTC/TDF, and 211 to the EFV/FTC/TDF arm. Baseline medians were as follows: GA, 21.9 weeks; HIV RNA, 903 copies/mL; and CD4 cell count, 466/μL. Insufficient weight gain was least frequent with DTG + FTC/TAF (15.0%) versus DTG + FTC/TDF (23.6%) and EFV/FTC/TDF (30.4%). Women in the DTG + FTC/TAF arm had the lowest rate of composite adverse pregnancy outcome. Low antepartum weight gain was associated with higher hazard of composite adverse pregnancy outcome (hazard ratio, 1.44 [95% confidence interval, 1.04-2.00]) and small size for GA (1.48 [.99-2.22]). More women in the DTG + FTC/TAF arm had a body mass index ≥25 (calculated as weight in kilograms divided by height in meters squared) at 50 weeks postpartum (54.7%) versus the DTG + FTC/TDF (45.2%) and EFV/FTC/TDF (34.2%) arms., Conclusions: Antepartum weight gain on DTG regimens was protective against adverse pregnancy outcomes typically associated with insufficient weight gain, supportive of guidelines recommending DTG-based ART for women starting ART during pregnancy. Interventions to mitigate postpartum weight gain are needed., Competing Interests: Potential conflicts of interest. R. M. H. is an Elsevier ClinicalKey editorial board member. R. M. H. also reports honoraria for lectures on this topic from the Los Angeles County Division of HIV and STI Programs and the UCLA CARE Center’s continuing medical education seminars. S. B. and L. Z. reports support for the present work from the NIH Division of AIDS/Eunice Kennedy Shriver National Institute of Child Health and Human Development and ViiV/GSK, paid to their institution. L. F. reports grants or contracts for the current study through NIH/IMPAACT. S. H. reports grants or contracts from UKZN Developing Research Innovation, Localisation and Leadership in South Africa (DRILL), the Fogarty International Center, the NIH Common Fund, Office of Strategic Coordination, Office of the Director, Office of AIDS Research, the NIH Office of the Director, the National Institute of Mental Health, NIH (award D43TW010131, paid to their institution, from January 2018 to July 2023), and the SA National Research Foundation (Thuthuka funding grant, paid to their institution, from January 2019 to December 2021). R. Z. reports receipt of study medication from ViiV healthcare for a federally funded research study (as principal investigator); ViiV is donating long-acting cabotegravir for an implementation study of preexposure prophylaxis in Botswana, funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. J. S. C. is a scientific advisor for Merck, participating on its advisory board, and reports royalties or licenses from UpToDate. P. S. reports grants or contracts from Gilead and ViiV; consulting fees from Gilead, Janssen, Merck, and ViiV; and participation on a data safety monitoring board or advisory board for Merck. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Microplastics (MPs), recognized as an emerging environmental menace, have been extensively investigated in both marine and terrestrial fauna. This study is comprehensive to investigate how polystyrene (PS) affects ruminant animals. The experimental design comprised 24 individually housed lambs, divided into a CON group (diet without PS) and three PS-exposed (25 μm, 50 μm, 100 μm) groups, each with six lambs, the exposure of PS was 100 mg/day, and the duration of exposure was 60 days. The study yielded noteworthy results: (ⅰ) PS leads to a decrease in average daily gain along with an increase in feed conversion rate. (ⅱ) PS decreases rumen ammonia nitrogen. The rumen microbiota diversity remains consistent. However, the relative abundance of Bacteroidetes and Actinobacteria increased in the PS-exposed groups, while the relative abundance of Coriobacteriales&#95;incertae&#95;Sedis and Prevotellaceae&#95;YAB2003&#95;group decreased. (ⅲ) PS leads to decrease in hemoglobin, thrombocytocrit, and albumin levels in lamb blood, thus triggering oxidative stress accumulation, along with swelling of the kidneys and liver. (ⅳ) PS inflicts severe damage to jejunum, consequently impacting digestion and absorption. (ⅴ) PS reduces meat quality and the nutritional value. In conclusion, PS-exposure inhibited lambs' digestive function, adversely affects blood and organs' health status, reducing average daily gain and negatively influencing meat quality. PS particles of 50-100 μm bring worse damage to lambs. This research aims to fill the knowledge void concerning MPs' influences on ruminant animals, with a specific focus on the meat quality of fattening lambs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic medication and may contribute to diabetes and coronary heart disease. To expand the unclear genetic mechanism underlying AIWG, we conducted a two-stage genome-wide association study in Han Chinese patients with schizophrenia. The study included a discovery cohort of 1936 patients and a validation cohort of 534 patients, with an additional 630 multi-ancestry patients from the CATIE study for external validation. We applied Mendelian randomization (MR) analysis to investigate the relationship between AIWG and antipsychotic-induced lipid changes. Our results identified two novel genome-wide significant loci associated with AIWG: rs10422861 in PEPD (P = 1.373 × 10 -9 ) and rs3824417 in PTPRD (P = 3.348 × 10 -9 ) in Chinese Han samples. The association of rs10422861 was validated in the European samples. Fine-mapping and functional annotation revealed that PEPD and PTPRD are potentially causal genes for AIWG, with their proteins being prospective therapeutic targets. Colocalization analysis suggested that AIWG and type 2 diabetes (T2D) shared a causal variant in PEPD. Polygenic risk scores (PRSs) for AIWG and T2D significantly predicted AIWG in multi-ancestry samples. Furthermore, MR revealed a risky causal effect of genetically predicted changes in low-density lipoprotein cholesterol (P = 7.58 × 10 -4 ) and triglycerides (P = 2.06 × 10 -3 ) caused by acute-phase of antipsychotic treatment on AIWG, which had not been previously reported. Our model, incorporating antipsychotic-induced lipid changes, PRSs, and clinical predictors, significantly predicted BMI percentage change after 6-month antipsychotic treatment (AUC = 0.79, R 2  = 0.332). Our results highlight that the mechanism of AIWG involves lipid pathway dysfunction and may share a genetic basis with T2D through PEPD. Overall, this study provides new insights into the pathogenesis of AIWG and contributes to personalized treatment of schizophrenia., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: To conduct a systematic review and meta-analysis with the aim of synthesizing existing data on the efficacy and safety of topiramate as an adjunctive treatment for reducing second-generation antipsychotic (SGA)-associated weight gain in children aged 4-18 years., Methods: We conducted a comprehensive search of PubMed, Embase, PsychNet and Web of Science from time of their inception up to 12 February 2024, including randomized controlled trials that compared SGA treatment with and without topiramate co-administration in children. The primary outcomes were changes in body weight and body mass index (BMI). Heterogeneity was assessed using I 2 statistics., Results: This systematic review included five randomized trials, totalling 139 participants (43.9% female; mean [SD] age 11.9 [3.5] years). Four of these trials were included in the meta-analysis, comprising 116 subjects. We found that topiramate was significantly effective both in reducing SGA-associated weight gain, with a mean difference of -2.80 kg (95% confidence interval [CI] -5.28 to -0.31; p = 0.037, I 2  = 86.7%) and a standardized mean difference (SMD) of -1.33 (95% CI -2.14 to -0.51; p = 0.014, I 2  = 31.7%), and in reducing BMI change compared to placebo (SMD -1.90, 95% CI -3.09 to -0.70; p = 0.02, I 2  = 0%). Sedation risk was lower with topiramate than with placebo (odds ratio 0.19, 95% CI 0.11-0.32; p < 0.01, I 2  = 0%). No significant differences were found in dropouts, any other side effects, and metabolic parameters, such as triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, and glucose. None of the included studies reported assessments on cognitive side effects., Conclusion: This meta-analysis suggests that topiramate is an effective and safe option for mitigating SGA-associated weight gain in children., (© 2024 John Wiley & Sons Ltd.)

Individualized lifestyle interventions using motivational interviewing (MI) approach are recommended for persons with severe mental illness (SMI) for effective weight management. The aim of this meta-analysis was to assess the effectiveness of various lifestyle interventions that addressed obesity among persons with SMI. Twelve RCTs were assessed by individual reviewers using revised cochrane risk-of-bias tool (RoB 2). The standardized mean difference (SMD) was calculated with a 95% CI. The age of participants was between 18 and 70 years. Waist circumference showed an SMD of -0.09 (-0.22, 0.03), weight -0.03 (-0.10, 0.15) and BMI -0.07 (-0.07, 0.22). The findings in this meta-analysis revealed that though lifestyle interventions were statistically insignificant in reducing antipsychotic induced weight gain among persons with SMI, they show changes in intervention group. Psychosocial management along with lifestyle interventions, and MI are effective in the management of antipsychotic induced weight gain., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This post hoc, pooled analysis examined the relationship between different weight gain categories and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving first-line platinum-based chemotherapy., Methods: Data were pooled from the control arms of three phase III clinical studies (NCT00596830, NCT00254891, and NCT00254904), and the maximum weight gain in the first 3 months from treatment initiation was categorised as >0%, >2.5%, and >5.0%. Cox proportional hazard modelling of OS was used to estimate hazard ratios (HRs) for each category, including baseline covariates, time to weight gain, and time to confirmed objective response (RECIST Version 1.0)., Results: Of 1030 patients with advanced NSCLC (IIIB 11.5% and IV 88.5%), 453 (44.0%), 252 (24.5%), and 120 (11.7%) experienced weight gain from baseline of >0%, >2.5%, and >5.0%, respectively. The median time to weight gain was 23 (>0%), 43 (>2.5%), and 45 (>5.0%) days. After adjusting for a time-dependent confirmed objective response, the risk of death was reduced for patients with any weight gain (>0% vs. ≤0% [HR 0.71; 95% confidence interval-CI 0.61, 0.82], >2.5% vs. ≤2.5% [HR 0.76; 95% CI 0.64, 0.91] and >5.0% vs. ≤5.0% [HR 0.77; 95% CI 0.60, 0.99]). The median OS was 13.5 versus 8.6 months (weight gain >0% vs. ≤0%), 14.4 versus 9.4 months (weight gain >2.5% vs. ≤2.5%), and 13.4 versus 10.2 months (weight gain >5.0% vs. ≤5.0%)., Conclusions: Weight gain during treatment was associated with a reduced risk of death, independent of tumour response. The survival benefit was comparable for weight gain >0%, >2.5%, and >5.0%, suggesting that any weight gain may be an early predictor of survival with implications for the design of interventional cancer cachexia studies., (© 2024 Pfizer Inc. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

In this study the efficacy of an intramuscular formulation of toltrazuril combined with gleptoferron for the control of porcine cystoisosporosis caused by Cystoisospora suis was investigated. The study was carried out on three Belgian farms with a confirmed history of C. suis infections. As none of the farms implemented a standardized toltrazuril treatment regimen for their piglets, the presence of resistant C. suis strains seems improbable. In total 90 litters, representing 1249 piglets, were included in the study and randomly allocated to either the treatment or control group. Piglets in the treatment group received a single intramuscular injection, containing 45 mg toltrazuril and 200 mg gleptoferron, between 1 and 3 days of age. Piglets in the control group received a single injection with only 200 mg gleptoferron. The effect of treatment on oocyst excretion, expressed in oocysts per gram of feces (OPG), average daily weight gain (ADG) and mortality was determined both pre- and post-weaning. A significant decrease in OPG as well as a decrease in the number of litters (pre-weaning) and pens (post-weaning) that tested positive for cystoisosporosis, was observed in the treated animals compared to the controls. Furthermore, treatment resulted in an increased ADG during the period from day 1 to day 21 (p-value: 0.03881). There was no significant difference in mortality observed between the treatment group to the control group (p-value: 0.2167). To our knowledge, this is the first report on the effect of toltrazuril on oocyst excretion after weaning. This finding highlights the potential long-term benefits of the treatment beyond the initial administration., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Bregt Decorte reports financial support was provided by CEVA Animal Health. Daniel Sperling reports a relationship with CEVA Animal Health that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As one of the most common antipsychotics, olanzapine may cause metabolic-related adverse effects, but it is still unknown how olanzapine alters lipid metabolism. In this study, we found that olanzapine-treated mice showed varying degrees of dyslipidemia, which was particularly pronounced in female mice. Based on ultra-performance liquid chromatography-quadrupole time-of-flight-MS (UPLC-Q-TOF-MS) technology and lipid metabolomics, we mapped the changes in lipid metabolism in olanzapine-treated mice and then compared the changes in lipid metabolism between male and female mice. There were 98 metabolic differentiators between the olanzapine-treated and control groups in females and 79 in males. These metabolites were glycerolipids, glycerophospholipids, fatty amides, and sphingolipids, which are involved in glycerolipid metabolism, glycerophospholipid metabolism, and fatty acid metabolism. These results suggest that olanzapine-induced changes in the levels of lipid metabolites are closely associated with disturbances in lipid metabolic pathways, which may underlie lipemia. This lipidome profiling study not only visualizes changes in lipid metabolism in liver tissue but also provides a foundation for understanding the regulatory pathways and mechanisms involved in olanzapine-induced lipid metabolism disorders. Furthermore, this study demonstrates differences in lipid metabolism between males and females, providing a reference for clinical treatment regimen selection., (© 2024 John Wiley & Sons Ltd.)

Integrase inhibitors and tenofovir alafenamide have become a mainstay in modern antiretroviral therapy; more recently, they have been implicated as causing increased weight gain beyond what may be expected with the "return to health" phenomenon. Some patients, namely those assigned female at birth, of the black race, or with lower baseline CD4 counts, may be more likely to experience weight gain. This review outlines existing evidence linking the agents to excessive weight as well as ongoing efforts to combat these effects., Competing Interests: Disclosure All authors: no reported conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Early-life stress and subsequent high-calorie diets during adolescence are known to be risk factors for developing metabolic and psychological disorders. Although non-nutritive sweeteners such as stevia and sucralose have been a useful alternative to reduce sugar consumption, the effects of prolonged consumption of these sweeteners on metabolism and behavior in adolescents remain unclear. Here, we evaluated the effects of early-stress followed by access to stevia or sucralose during adolescence on weight gain, glycemia, and anxiety-related behaviors in male and female rats. During postnatal days (PNDs) 1-21, pups were separated twice a day, for 180 min each time, from their dam nest while non-separated pups served as controls. The pups were weaned, separated by sex and randomly distributed into the stevia, sucralose and water conditions. During PNDs 26-50, two bottles containing water and stevia or sucralose were placed in the animal home-cages, and body weight and blood glucose measures were scored. On PNDs 50 and 51, behavioral measures were obtained in the open-field test. Results showed that male rats consuming stevia reduced body weight gain, blood glucose and increased locomotion. Early-stress led to low blood glucose and alterations in anxiety and locomotion-related behaviors in a sex-dependent manner. Moreover, sucralose access during adolescence reversed the effects of early-stress on anxiety-related behaviors in female rats. The results suggest that the consumption of stevia and sucralose could be an alternative for the replacement of sugar-sweetened beverages, especially in adolescents who have had adverse early-life experiences., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest regarding this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Cystic fibrosis (CF) is caused by CF transmembrane conductance regulator (CFTR) gene mutations producing dysfunctional CFTR proteins leading to progressive clinical disease. Elexacaftor-tezacaftor-ivacaftor (ETI) remarkably improves lung disease but is associated with substantial weight gain., Study Design and Methods: We performed a single-center longitudinal study predicting 6-month weight gain after ETI initiation. We used linear mixed effects modeling (LME) to determine association of ETI treatment with changing body mass index (BMI). Using linear regression, we examined BMI prediction models with distinct combinations of main effects to identify a model useful for patient counseling. We used up to eight commonly observed clinical characteristics as input variables (age, sex, percent predicted FEV1 [FEV1%], F508del homozygous state, pancreatic sufficiency, HgbA1c, prior modulator use and prior year number of pulmonary exacerbations)., Results: We evaluated 154 patients (19-73 years old, 54% female, FEV 1 % = 19-121, 0-6 prior year pulmonary exacerbations). LME demonstrated an association between ETI use and weight increases. Exhaustive testing suggested a parsimonious linear regression model well-fitted to data that is potentially useful for counseling. The two variable model shows that on average, BMI decreases by 0.045 (95% Confidence Interval [CI] = -0.069 to -0.021, p < 0.001) for every year of age and increases by 0.322 (CI = 0.142 to 0.502, p = 0.001) for each additional prior year exacerbation at the time of ETI initiation., Interpretation: Young patients with many prior year pulmonary exacerbations likely have the largest 6 month weight gain after starting ETI., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Purpose of Review: Insomnia and short sleep have been linked with weight gain and obesity. However, these findings have not been consistent across studies. We review recent evidence for the association between insomnia, short sleep, and weight gain, as well as the relationship between behavioral and pharmacological treatments for sleep and weight., Recent Findings: The relationship between insomnia and obesity is mixed, with stronger associations between insomnia with short sleep and obesity than other presentations of insomnia. Short sleep is associated with weight gain. Z-drugs and benzodiazapines do not appear to impact weight, but many antidepressants and antipsychotics that are used for insomnia treatment do cause weight gain. The relationships between insomnia and short sleep with weight gain and obesity are inconsistent. More prospective trials are needed to identify mediators and moderators of this relationship to better develop and deliver effective interventions for both sleep and weight problems., (© 2024. The Author(s).)

Purpose of Review: The purpose of this review is two-fold: (1) to discuss a case report of idiopathic intracranial hypertension (IIH) after abrupt cessation of a glucagon-like peptide-1 (GLP-1) receptor agonist with resultant rapid weight gain and (2) to review the literature regarding the potential role of GLP-1 receptor agonists in the treatment of IIH as well as potential pitfalls., Recent Findings: GLP-1 receptor agonists have become widely used to treat obesity. Obesity is a known risk factor for the development of IIH, though the precise pathophysiology is unclear. GLP-1 receptor agonists may help treat IIH by promoting weight loss, lipolysis of adipose tissue, and potentially decreasing the secretion of CSF, as was seen in rat models. Abrupt cessation of GLP-1 receptor agonists can result in regaining lost weight rapidly. In the case that we present, the patient stopped duraglutide abruptly due to lack of insurance coverage and regained the weight she had lost within a month. She subsequently developed IIH. GLP-1 receptor agonists have the potential to help treat IIH; however, this class of medication needs to be used carefully, as cessation of the medication and resultant rapid weight gain can result in IIH., (© 2024. The Author(s).)

Background: The introduction of dolutegravir (DTG) in treating HIV has shown enhanced efficacy and tolerability. This study examined changes in weight gain and body mass index (BMI) at 6- and 12-months after post-initiating antiretroviral therapy (ART), comparing people living with HIV (PLHIV) on DTG-based regimens with those on non-DTG-based regimens in Malawi., Methods: Retrospective cohort data from 40 public health facilities in Malawi were used, including adult ART patients (aged ≥ 15 years) from January 2017 to March 2020. The primary outcomes were BMI changes/transitions, with secondary outcomes focused on estimating the proportion of mean weight gain > 10% post-ART initiation and BMI category transitions. Descriptive statistics and binomial regression were used to estimate the unadjusted and adjusted relative risks (RR) of weight gain of more than ( >) 10%., Results: The study included 3,520 adult ART patients with baseline weight after ART initiation, predominantly female (62.7%) and aged 25-49 (61.1%), with a median age of 33 years (interquartile range (IQR), 23-42 years). These findings highlight the influence of age, ART history, and current regimen on weight gain. After 12months follow up, compared to those aged 15-24 years, individuals aged 25-49 had an Adjusted RR (ARR) of 0.5 (95% Confidence Interval (CI): 0.35-0.70), suggesting a 50% reduced likelihood of > 10% weight gain after post-ART initiation. Similarly, those aged 50 + had an ARR of 0.33 (95% CI: 0.20-0.58), indicating a 67% decreased likelihood compared to the youngest age group 15-24 years. This study highlights the positive impact of DTG-based regimens, revealing significant transitions from underweight to normal BMI categories at 6- and 12-months post-initiation., Conclusion: This study provides insights into weight gain patterns in patients on DTG-based regimens compared with those on non-DTG regimens. Younger individuals (15-24 years) exhibited higher odds of weight gain, suggesting a need for increased surveillance in this age group. These findings contribute to the understanding DTG's potential effects on weight gain, aiding clinical decision making. Further research is required to comprehensively understand the underlying mechanisms and long-term implications of weight gain in patients receiving DTG-based regimens., (© 2024. The Author(s).)

Background: Synthesizing current evidence on interventions to improve survival outcomes in preterm infants is crucial for informing programs and policies. The objective of this study is to investigate the impact of topical emollient oil application on the weight of preterm infants., Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. To identify relevant studies, comprehensive searches were conducted across multiple databases, including PubMed, Cochrane, Scopus, Clinical trials, ProQuest Central, Epistemonikos, and gray literature sources. The inclusion criteria were based on the PICO (Population, Intervention, Comparison, and Outcomes) format. Study quality was assessed using the Cochrane risk of bias tool for randomized trials (RoB 2.0). Data analysis was performed using StataCrop MP V.17 software, which included evaluating heterogeneity, conducting subgroup analysis, sensitivity analysis, and meta-regression. The findings were reported in accordance with the PRISMA checklist, and the review was registered with PROSPERO (CRD42023413770)., Results: Out of the initial pool of 2734 articles, a total of 18 studies involving 1454 preterm neonates were included in the final analysis. Fourteen of these studies provided data that contributed to the calculation of the pooled difference in mean weight gain in preterm neonates. The random effects meta-analysis revealed a significant pooled difference in mean weight gain of 52.15 grams (95% CI: 45.96, 58.35), albeit with high heterogeneity (I2 > 93.24%, p 0.000). Subgroup analyses were conducted, revealing that preterm infants who received massages three times daily with either sunflower oil or coconut oil exhibited greater mean differences in weight gain. Meta-regression analysis indicated that the type of emollient oil, duration of therapy, and frequency of application significantly contributed to the observed heterogeneity. A sensitivity analysis was performed, excluding two outlier studies, resulting in a pooled mean weight difference of 78.57grams (95% CI: 52.46, 104.68). Among the nine studies that reported adverse events, only two mentioned occurrences of rash and accidental slippage in the intervention groups., Conclusion: The available evidence suggests that the application of topical emollient oil in preterm neonates is likely to be effective in promoting weight gain, with a moderate-to-high level of certainty. Based on these findings, it is recommended that local policymakers and health planners prioritize the routine use of emollient oils in newborn care for preterm infants. By incorporating emollient oils into standard care protocols, healthcare providers can provide additional support to promote optimal growth and development in preterm infants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Getaneh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Obesity is considered the leading public health problem in the medical sector. The phenotype includes overweight conditions that lead to several other comorbidities that drastically decrease health. Glucagon-like receptor agonists (GLP-1RAs) initially designed for treating type 2 diabetes mellitus (T2DM) had demonstrated weight loss benefits in several clinical trials . In vivo studies showed that GLP-1RA encourages reduced food consumption and consequent weight reduction by stimulating brown fat and enhancing energy outlay through the action of the sympathetic nervous system (SNS) pathways. Additionally, GLP-1RAs were found to regulate food intake through stimulation of sensory neurons in the vagus, interaction with the hypothalamus and hindbrain, and through inflammation and intestinal microbiota. However, the main concern with the use of GLP-1RA treatment was weight gain after withdrawal or discontinuation. We could identify three different ways that could lead to weight gain. Potential factors might include temporary hormonal adjustment in response to weight reduction, the central nervous system's (CNS) incompetence in regulating weight augmentation owing to the lack of GLP-1RA, and β -cell malfunction due to sustained exposure to GLP-1RA. Here, we also review the data from clinical studies that reported withdrawal symptoms. Although the use of GLP-1RA could be beneficial in multiple ways, withdrawal after years has the symptoms reversed. Clinical studies should emphasize the downside of these views we highlighted, and mechanistic studies must be carried out for a better outcome with GLP-1RA from the laboratory to the bedside., Competing Interests: The author declares that there are no conflicts of interest., (Copyright © 2024 Ibrahim Abdullah bin Ahmed.)

Cancer cachexia causes anorexia and metabolic disorders, eventually leading to sarcopenia, which in turn contributes to the development of functional disabilities. Although anamorelin hydrochloride tablets are marketed to treat cancer cachexia, their efficacy varies significantly among patients. Here, we investigated the efficacy of anamorelin and the factors associated with weight gain. The factors that contributed to weight gain in patients before starting anamorelin were as follows: the patients' disease stage had not progressed to refractory cachexia based on the cancer cachexia classification of the European Palliative Care Research Collaborative; the patients had received fewer lines of anticancer treatment at the start of oral administration of anamorelin; and the patients had not met all the criteria for starting treatment with anamorelin, namely, C-reactive protein level >0.5 mg/dL, hemoglobin level <12 g/dL, and albumin level <3.2 g/dL. These results suggest that early administration of anamorelin hydrochloride tablets may increase the response rate when cancer cachexia is diagnosed.

Nonhuman primates used in biomedical research may experience clinically significant weight loss for a variety of reasons. Episodes of anorexia (complete loss of appetite) or hyporexia (decreased appetite) can result in significant weight loss, potentially altering animal welfare and scientific studies. The FDA has approved several appetite stimulants for use in domestic species, but currently none are approved for use in NHP. Treatment of inappetence and weight loss in NHP often relies on the extralabel use of these compounds. Capromorelin is a ghrelin receptor agonist. As a growth hormone secretagogue, capromorelin increases appetite, leading to weight gain. Studies in several species have shown a positive correlation between capromorelin administration and weight gain; in 2017, an oral solution of capromorelin received FDA approval for use in dogs. We tested this solution in healthy adult rhesus macaques (n = 3 males and 3 females) for its effects on body weight and insulin like growth factor-1 (IGF-1). A control group (n = 2 males and 2 females) was used for comparison. Treated macaques received a 3mg/kg oral dose daily for 7 d. Clinical signs were observed daily. Weights were collected before, during and at the end of treatment. Blood was drawn before, during and after treatment for measurement of IGF-1 levels and standard hematology and biochemistry parameters. Baseline-adjusted mean body weights and IGF-1 levels were significantly higher in treated as compared with control monkeys after 7 d of beginning treatment (body weight of 10.5±0.1kg (mean ± SEM) and 10.1±0.1kg, respectively; IGF-1 of 758±43ng/mL and 639±22ng/mL, respectively). Capromorelin administration was not associated with appreciable changes in hematologic and biochemical values in treated macaques. These findings suggest that capromorelin may be useful for treating inappetence and weight loss in NHP, and based on blood analysis, a 7-d course of treatment does not appear to cause acute toxicity.

Scope: Higher intake of cruciferous and allium vegetables is associated with lower cardiometabolic risk. Little research has investigated the cardiometabolic effects of S-methyl cysteine sulfoxide (SMCSO), found abundant in these vegetables. This study hypothesizes that SMCSO will blunt development of metabolic syndrome features in mice fed high-fat feed., Methods and Results: Fifty C57BL/6 male mice are randomly assigned to standard-chow, high-fat, or high-fat supplemented with low-SMCSO (43 mg kg -1 body weight [BW] day -1 ), medium-SMCSO (153 mg kg -1 BW day -1 ), or high-SMCSO (256 mg kg -1 BW day -1 ) for 12-weeks. High-fat with SMCSO did not prevent diet-induced obesity, glucose intolerance, or hypercholesterolemia. Mice fed high-fat with SMCSO has higher hepatic lipids than mice fed standard-chow or high-fat alone. Urinary SMCSO increases at 6- and 12-weeks in the low-SMCSO group, before reducing 46% and 28% in the medium- and high-SMCSO groups, respectively, at 12-weeks, suggesting possible tissue saturation. Interestingly, two SMCSO-fed groups consume significantly more feed, without significant weight gain. Due to limitations in measuring consumed feed, caution should be taken interpreting these results., Conclusion: SMCSO (43-256 mg kg -1 BW day -1 ) does not ameliorate metabolic syndrome features in high-fat fed mice. Substantial knowledge gaps remain. Further studies should administer SMCSO separately (i.e., gavage), with metabolic studies exploring tissue levels to better understand its physiological action., (© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)

Background: As many as 60% of pediatric patients taking second-generation antipsychotics (SGA) experience weight gain (antipsychotic-induced weight gain). However, the subgroup that experienced substantial weight increase was poorly understood. This study aimed to identify the development and predictors of clinically significant weight gain (CSWG) among pediatric SGA recipients. Methods: A retrospective analysis of the 2016 to 2021 IQVIA Ambulatory EMR-US database was conducted. The study cohort comprised SGA-naive patients ages 5 to 19, continuously prescribed SGA for ≥90 days. CSWG was defined as a weight gain in BMI z -score >0.5. The development of CSWG was described using the group-based trajectory model approach, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the CSWG trajectories. Results: Of the 16,262 SGA recipients who met the inclusion criteria, 4 distinctive CSWG trajectories were identified: (1) Rapid (14.6%), (2) Gradual (12.6%), (3) Transit (7%), and (4) no CSWG (65.8%). Factors associated with a higher likelihood of having rapid or gradual CSWG versus nonsignificant weight gain were being younger (OR [95% CI] = 12-17 vs. 5-11, Rapid, 0.727 [0.655-0.806]; Gradual, 0.776 [0.668-0.903]), male (Rapid, 1.131 [1.021-1.253]), non-Hispanic White (Black vs. White: Rapid, 0.833 [0.709-0.98]), with lower baseline BMI z -score (Rapid, 0.376 [0.361-0.392]; Gradual, 0.449 [0.424-0.476]), and receiving olanzapine as the initial SGA (Rapid, 1.38 [1.093-1.74]). The Area under the Receiver operating characteristic (ROC) Curve for the comparison of rapid and gradual CSWG with no CSWG trajectory were 0.83 and 0.80, respectively. Conclusions: SGA recipients experienced four distinctive CSWG trajectories (Rapid, Gradual, Transient, and No CSWG). The risk of CSWG could be predicted using patient characteristics at the SGA initiation. This insight highlights the importance of personalized monitoring and timely intervention strategies for at-risk individuals who experienced persistent CSWG in real practice.

Background: Integrase strand-transfer inhibitors (INSTIs) and tenofovir alafenamide have been associated with weight gain in several clinical trials and observational cohorts. However, whether weight gain associated with INSTIs and tenofovir alafenamide confers a higher risk of weight-related clinical events is unclear. We aimed to assess whether changes in BMI differentially increase hypertension or dyslipidaemia risk in people with HIV receiving INSTIs, tenofovir alafenamide, or both versus other contemporary regimens., Methods: This multicentre, prospective observational study analysed prospective data from RESPOND, an international consortium of HIV cohorts for which recruitment began in 2017 and is still ongoing from HIV clinics and hospitals in 37 European countries and Australia. Participants were eligible if they were aged 18 years or older, receiving INSTI-containing antiretroviral therapy (ART) regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. We excluded participants without baseline CD4 or HIV RNA results and those receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues. They were followed up from baseline until the earliest hypertension or dyslipidaemia event, their last visit, or Dec 31, 2021, whichever was earlier. The primary outcomes were incidence of hypertension and dyslipidaemia, for which we used multivariable Poisson regression adjusted for time-updated BMI to determine unadjusted and adjusted incidence rate ratios (IRRs) of hypertension and dyslipidaemia in people receiving INSTIs, tenofovir alafenamide, or both, and tested for interaction between time-updated ART regimen and BMI., Findings: Of the 35 941 RESPOND participants, 9704 (7327 [75·5 %] male and 2377 [24·5%] female) were included in the hypertension analysis and 5231 (3796 [72·6%] male and 1435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54-1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30-1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31-1·68) or without (1·25, 1·13-1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10-1·40) and tenofovir alafenamide alone (1·22, 1·03-1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07-1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96-1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (p interaction =0·46 for hypertension; p interaction =0·31 for dyslipidaemia)., Interpretation: Although residual confounding cannot be entirely excluded, the use of INSTIs was associated with incident hypertension, and the use of tenofovir alafenamide was associated with dyslipidaemia, with the latter association partly mediated by weight gain. These results reiterate the need for hypertension and dyslipidaemia screening in people with HIV., Funding: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences., Competing Interests: Declaration of interests AM has received travel support and lecture and consultancy fees from Gilead Sciences, ViiV Healthcare, Eiland, and Bonnin, all outside the submitted work. VV is an employee of and has stocks in ViiV Healthcare. CC is an employee of and has stocks in Gilead Sciences. EB is an employee of and has stocks in MSD. ML has received sitting fees from Certa Therapeutics data safety monitoring board. KG-P has served on advisory boards and provided lectures for Gilead Sciences and ViiV Healthcare. AR has received support for attending meetings and travel from Gilead Sciences and Pfizer, received an investigator-initiated trial grant from Gilead Sciences, and participated on a data safety monitoring board or advisory board for MSD and Pfizer (all paid to the institution). All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The mechanisms by which antipsychotic medications (APs) contribute to obesity in schizophrenia are not well understood. Because AP effects on functional brain connectivity may contribute to weight effects, the current study investigated how AP-associated weight-gain risk relates to functional connectivity in schizophrenia., Methods: Fifty-five individuals with schizophrenia (final N = 54) were divided into groups based on previously reported AP weight-gain risk (no APs/low risk [N = 19]; moderate risk [N = 17]; high risk [N = 18]). Resting-state functional magnetic resonance imaging (fMRI) was completed after an overnight fast ("fasted") and post-meal ("fed"). Correlations between AP weight-gain risk and functional connectivity were assessed at the whole-brain level and in reward- and eating-related brain regions (anterior insula, caudate, nucleus accumbens)., Results: When fasted, greater AP weight-gain risk was associated with increased connectivity between thalamus and sensorimotor cortex (pFDR = 0.021). When fed, greater AP weight-gain risk was associated with increased connectivity between left caudate and left precentral/postcentral gyri (pFDR = 0.048) and between right caudate and multiple regions, including the left precentral/postcentral gyri (pFDR = 0.001), intracalcarine/precuneal/cuneal cortices (pFDR < 0.001), and fusiform gyrus (pFDR = 0.008). When fed, greater AP weight-gain risk was also associated with decreased connectivity between right anterior insula and ventromedial prefrontal cortex (pFDR = 0.002)., Conclusions: APs with higher weight-gain risk were associated with greater connectivity between reward-related regions and sensorimotor regions when fasted, perhaps relating to motor anticipation for consumption. Higher weight-gain risk APs were also associated with increased connectivity between reward, salience, and visual regions when fed, potentially reflecting greater desire for consumption following satiety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This study examined the effects of using mushroom mycelium to ferment tigernut and cassava pulp on the growth performance, haematology and immunology of rabbits. Seventy-five New Zealand Bulk grower rabbits were randomly distributed to four treatment groups and a control group in a completely randomized approach. The treatment groups were fed with formulated experimental diets containing one of fermented tigernut drink by-product (FT), fermented cassava sievate (FC), unfermented tigernut drink by-product (UT), or unfermented cassava sievate (UC). The control group was fed a basal diet with no additives. The proximate composition of the fermented feed was analyzed. The weight gain of the animals was, 834.5, 633, 790, 510, and 706 g for control, FT, FC, UT, and UC respectively. The packed cell volume (PCV) for animals in the control group, FT, and FC are 34.33, 37.26, and 32.29% respectively. The red blood cell (RBC) of the FT was favourably improved (5.53 × 10 12 /L) compared to those of UT (2.28 × 10 12 /L), while there was a reduction in the red blood cell count of FC group (1.02 × 10 12 /L). Conclusively, the inclusion of fermented tiger nut drink by-product in rabbit feed improved the PCV and RBC of the rabbits' understudy but did not affect their growth performance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction-Aim: Flexible insulin therapy is currently considered the gold standard therapy of type 1 diabetes. We aimed to study the evolution of glycemic control, weight and nutritional intake of a group of patients with type 1 diabetes, three months after the initiation of functional insulin therapy (FIT)., Methods: This was a prospective longitudinal study having included 30 type 1 diabetic patients hospitalized for education to FIT. Each patient underwent an assessment of glycemic control (glycated hemoglobin (A1C) and number of hypoglycemia), weight and nutritional intake before FIT and 3 months after the initiation of this educative approach., Results: The mean age of patients was 21,8 ± 7,9 years and the sex ratio was 0,5. The mean duration of diabetes was 7,2 ± 6 years. Three months after initiation of FIT, we observed a significant lowering of A1C, which went from 9,2 ± 1,6% to 8,3 ± 1,4% (p<0,001) of the number of minor hypoglycemia (p=0,001) and that of severe hypoglycemia (p= 0,021). the average weight went from 64,6 ± 13,1 kg to 65,5 ± 13,5 kg (p = 0,040) with a significant increase in BMI (p = 0,041). Weight gain was observed in 67% of patients. This weight gain contrasted with a significant decrease in caloric (p = 0,040) and in carbohydrates intakes (p = 0,027)., Conclusion: Weight gain, associated with better glycemic control, should encourage the healthcare team to strengthen therapeutic education of patients undergoing FIT in order to limit weight gain.

A total of 480 newly weaned pigs (PIC 337 × 1050; Genus, Hendersonville, TN) with an initial body weight (BW) of 6.20 ± 0.61 kg were used in a dose-response study to investigate the impact of increasing standardized ileal digestible (SID) Arg:Lys on nursery pig growth performance. At weaning, pigs were placed into 48 pens with 5 barrows and 5 gilts per pen. Pens were randomly assigned to 1 of 6 dietary treatments. The experimental diets were formulated with increasing SID Arg:Lys, achieved by substituting corn starch, glycine, and l-alanine with l-arginine, resulting in SID Arg:Lys ranging from 45% to 145%. Diets were sublimiting in SID Lys and exceeded all other essential amino acid requirements. The experimental diets were fed across two feeding phases from days 0 to 10 and 10 to 27, with adjustments made to account for the Lys requirement of the pigs. All pens were placed on a common diet for the remaining 14 d of the study to evaluate carryover effects. Pigs and feeders were weighed at the start and end of each phase to calculate average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (G:F). Data were analyzed according to a linear regression model, which included the linear and quadratic effects of SID Arg:Lys and initial BW. Pen was the experimental unit, and results were considered significant at P ≤ 0.05 and a tendency at 0.50 < P ≤ 0.10. From days 0 to 27, Arg:Lys tended to have a quadratic effect on ADFI (P = 0.058), where 97.00 ± 7.631% SID Arg:Lys maximized feed intake. Similarly, Arg:Lys had a quadratic impact on ADG (P = 0.046), where ADG was maximized at a SID Arg:Lys of 95.65 ± 7.165. Correspondingly, Arg:Lys had a quadratic effect on pig BW on day 27 (P = 0.014). These effects were carried through the end of the study, where Arg:Lys quadratically impacted days 0 to 41 ADFI (P = 0.006), ADG (P = 0.077), and day 41 BW (P = 0.028). There was no evidence of an effect of SID Arg:Lys on G:F throughout the study (P ≥ 0.315). In conclusion, SID Arg:Lys quadratically impacted ADFI and ADG in 6- to 13-kg nursery pigs, where ADFI was maximized at a SID Arg:Lys of 97.00% (95% CI [81.6%, 112.4%]), and ADG was maximized at a SID Arg:Lys of 95.65% (95% CI [81.2%, 110.1%]). Together, these data suggest that the SID Arg:Lys requirement of nursery pigs is at least 81%, based on the lower bounds of the 95% CI for maximum ADG and ADFI, and excessive Arg supplementation may negatively affect growth performance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Research on sex differences has increased across various fields, including cancer and its treatment domains. Reports have indicated sex differences in cancer incidence, survival rates, and the efficacy of anticancer drugs. However, such reports are limited, and in-depth assessments of the underlying mechanisms are still in progress. Although various chemotherapeutic regimens are applicable for breast cancer treatment, reports have surfaced regarding weight gain in female patients undergoing fluorouracil, epirubicin, cyclophosphamide (FEC) or cyclophosphamide, methotrexate, fluorouracil (CMF) therapy. We hypothesized the potential of 5-fluorouracil (5-FU) in weight gain and sex-related differences. To address this, we conducted experiments in mice to confirm weight gain and sex differences following 5-FU administration, and elucidate the underlying mechanisms. Our findings revealed weight gain and increased food intake in female mice following 5-FU administration. Additionally, female mice receiving 5-FU exhibited increased norepinephrine and α1- and α2-adrenergic receptor expression, reduced estradiol levels, and increased ghrelin levels. These results indicate 5-FU administration-induced sex differences in weight gain and implicate increased food intake because of increased norepinephrine and α1- and α2-adrenergic receptor expression, reduced estradiol levels, and a subsequent increase in ghrelin levels, which contribute to weight gain in female patients undergoing CMF therapy.

This study evaluated the effects of supplementation with Antrodia cinnamomea mycelium by-product (ACBP) on growth performance and immune response in weaning piglets. Total available content and antioxidant capacity of ACBP were determined. Ninety-six black pigs were randomly distributed to 24 pens. Study compared four groups which were supplemented with ACBP at 0%, 2.5%, 5%, or 10% for 6 weeks after weaning at 4 weeks. Results showed that ACBP on total phenolic, total flavonoid, and total triterpenoids contents were 13.68 mg GAE/g DW, 1.67 μg QE/g DW, and 15.6 mg/g, respectively. Weaning piglets fed 2.5% ACBP showed a significant decreased body weight gain compared with those supplemented with 5% ACBP, 10% ACBP, and control groups. Results showed that all ACBP groups increased the villi height of jejunum significantly. Incidence of diarrhea in 11 weeks with supplementation with 5% and 10% ACBP diets were lower than in control group. The 10% ACBP group showed significantly lower expression of immune response genes (IL-1β, IL-6, IL-8, TNF-α, and IFN-γ) than the 2.5% and 5% ACBP groups. Based on results, dietary supplementation with 10% ACBP did not significantly affect body weight but could decrease piglet diarrhea condition and expression of IL-1β and IL-6 genes., (© 2024 Japanese Society of Animal Science.)

Oleuropein aglycone (OA), which is the absorbed form of oleuropein, is a major phenolic compound in extra virgin olive oil. We analyzed the anti-obesity effect of OA intake combined with mild treadmill walking (MTW, 4 m/min for 20 min/d, 5-6 d/wk, without electric shocks and slope) in rats under a high-fat diet (HF). Four-week-old male Sprague-Dawley rats (n=28) were equally divided into four groups: control (HF), 0.08% oleuropein-supplemented HF (HFO), HF with MTW (HF+W), and HFO with MTW (HFO+W) groups. After 28 d, the inguinal subcutaneous fat content and weight gain were significantly lower in the HFO+W group than in the control group. The HFO+W group also had significantly higher levels of urinary noradrenaline secretion, interscapular brown adipose tissue, uncoupling protein 1, brain transient receptor potential ankyrin subtype 1 (TRPA1), vanilloid subtype 1 (TRPV1), and brain-derived neurotrophic factor (BDNF) than the control group. Especially, the HFO+W group showed a synergistic effect on noradrenaline secretion. Therefore, OA combined with MTW may accelerate the enhancement of UCP1 and BDNF levels in rats with HF-induced obesity by increasing noradrenaline secretion after TRPA1 and TRPV1 activation.

The consumption of non-nutritive sweeteners (NNS) is on the rise among different populations. In parallel, the debate about their potential health benefits and risks remains inconclusive. Numerous published studies elucidate the impact of NNS on general health, weight control, and the risk of certain diseases. However, no definitive conclusions regarding the effect of chronic NNS use on weight have been reached in humans. This review summarizes current evidence related to the biological role of NNS and their subsequent effects on weight. The mechanisms of action through which NNS impact weight are discussed, including their effect on sweet taste receptors, cognition, metabolic and endocrine functions, intestinal microbiota, and adiposity. Conflicting evidence is hindering the formulation of precise recommendations, but the evidence opposing the use of NNS remains weak, and the ultimate impact on weight largely relies on several other behavioral patterns., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose of Review: Antiretroviral therapy (ART) has long been implicated in fat alterations and weight variations leading to cardiometabolic consequences. Recent largely prescribed antiretrovirals (ARVs) from the integrase-strand-transfer-inhibitor (INSTI) class have been associated with excessive weight gain/obesity in a minority of persons with HIV (PWH). As well, in the nucleoside reverse transcriptase inhibitors (NRTI) class, tenofovir-alafenamide (TAF), often replacing tenofovir-disoproxil-fumarate (TDF), has been associated with weight gain, a worrying concern in the present worldwide obesogenic environment. The respective role of the different ARV, the risk factors and the mechanisms remain questionable., Recent Findings: The INSTIs dolutegravir (DTG) and bictegravir (BIC) and TAF have a proper effect on weight gain, while efavirenz (EFV) and TDF inhibit it. These effects are reported in ART-naïve PWH, in addition to weight gain resulting from the return to health process, and in ART-controlled PWH. Also, INSTIs induce weight gain in adolescents and excessive weight gain during pregnancy. The effects of INSTIs and TAF are additive. Their trajectory differs. Most of the weight gain is observed during the initial 12-month period.The main risk factors are low CD4+ and high viral load (VL) in ART-naïve PWH, Black race or originating from some African countries and female gender. The role of age and BMI differs between studies. The reversibility of the effect of INSTI and TAF appears limited.Regarding the mechanisms, the INSTIs can directly alter adipose tissue in particular through inhibition of fat beiging, resulting in fat fibrosis and hypertrophy. Macrophage infiltration is decreased. The mechanisms explaining the opposite effects of TDF and TAF remain elusive., Summary: The specific impact of DTG, BIC and TAF on weight gain/obesity in PWH is confirmed in different populations independently of the weight limiting effect of EFV and TDF. ART-linked excessive weight gain is uncommon. African origin and female sex are risk factors that need to be considered. The mechanisms are better understood for INSTIs but unknown for TDF/TAF. The reversibility of weight gain/obesity when stopping INSTI or TAF remains limited., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects., Methods: Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets., Results: FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group., Conclusion: The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The active season of hibernators corresponds to rapid adiposity in preparation for the next hibernation season. We have previously shown that this dramatic increase in adipose mass is associated with metabolic inflammation similar to what is seen in obesity and metabolic disease. We next sought to determine whether curbing this inflammation at its source (i.e., the gut) would attenuate weight gain in fattening 13-lined ground squirrels ( Ictidomys tridecemlineatus ). We fed active yearling ground squirrels a diet containing the gut-specific nonsteroidal anti-inflammatory drug mesalazine (5-aminosalicylic acid) for 10 wk. Mesalazine treatment had slight effects on microbial community diversity in the cecum and colon. Not surprisingly, mesalazine treatment decreased inflammatory cytokine levels in the ileum and colon. Mesalazine also decreased proinflammatory and increased anti-inflammatory cytokines in omental white adipose tissue (oWAT). Despite this, body mass was unaffected, and caloric intake increased in mesalazine-treated squirrels, mainly in males. Mass of the primary WAT depot, intra-abdominal WAT (iaWAT), or the highly metabolic oWAT were unaltered by treatment, as was adiposity index. Together, these results suggest that mesalazine treatment has some effects on adiposity in fattening ground squirrels, but this treatment needs to be modified to overcome the strong drive to fatten in this species. NEW & NOTEWORTHY Adiposity and obesity are caused, at least in part, by inflammation of metabolic tissues. Hibernators, like ground squirrels, undergo this same metabolic inflammation during their summer fattening period. We attempted to curb this inflammation, and thus fattening, using mesalazine. We found that mesalazine did curb the inflammation but did not affect fattening, likely due to the strong drive to fatten in hibernators.

Objective: We aimed to determine the reversibility of at least 7% weight gain within 12 months following tenofovir alafenamide (TAF) and/or integrase strand transfer inhibitor (INSTI) discontinuation in people with HIV (PWH) from the Dutch ATHENA cohort., Design and Methods: PWH with at least 7% weight gain within 24 months after first switch to TAF and/or INSTI whilst being virally suppressed were selected, excluding those with comorbidities/co-medication known to be associated with weight gain. PWH who discontinued only TAF, only INSTI or TAF+INSTI, with available follow-up weight, were included. Mean weight change in the 24 months prior to and 12 months after discontinuation was modelled using mixed-effects linear regression. Factors associated with yearly weight change were assessed using linear regression., Results: In 115 PWH, discontinuing only TAF ( n  = 39), only INSTI ( n  = 53) or TAF+INSTI ( n  = 23), the adjusted mean modelled weight change in the 24 months prior to discontinuation was +4.50 kg [95% confidence interval (CI) 3.04-6.10], +4.80 kg (95% CI 2.43-7.03) and +4.13 kg (95% CI 1.50-7.13), respectively, and -1.89 kg (95% CI -3.40 to -0.37), -1.93 kg (95% CI -3.92 to +0.07) and -2.55 kg (95% CI -5.80 to +0.02) in the 12 months postdiscontinuation. A greater number of years since HIV diagnosis was associated with greater reversibility of weight gain. No associations were found between weight change postdiscontinuation and changes in NRTI backbone or anchor agent at moment of discontinuation., Conclusion: There was no evidence of rapid reversibility of at least 7% TAF-associated and/or INSTI-associated weight gain after discontinuation of these agents. Studies of larger and more diverse populations of PWH are required to more fully understand the degree to which weight gain is reversible when discontinuing TAF and/or INSTI., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The most common causes of death in schizophrenia are cardiovascular disorders, which are closely related to metabolic syndrome/obesity. To better understand the development of metabolic alterations early in the course of illness, we quantified daily medication exposure in the first days of the first hospitalization for psychosis and related it to changes in weight and metabolic markers., Study Design: We recruited participants with first episode psychosis (FEP, N = 173) during their first psychiatric hospitalization and compared them to controls (N = 204). We prospectively collected weight, body mass index, metabolic markers, and exact daily medication exposure at admission and during hospitalization., Study Results: Individuals with FEP gained on average 0.97 ± 2.26 BMI points or 3.46 ± 7.81 kg of weight after an average of 44.6 days of their first inpatient treatment. Greater antipsychotic exposure was associated with greater BMI increase, but only in people with normal/low baseline BMI. Additional predictors of weight gain included type of medication and duration of treatment. Medication exposure was not directly related to metabolic markers, but higher BMI was associated with higher TGC, TSH, and lower HDL. Following inpatient treatment, participants with FEP had significantly higher BMI, TGC, prolactin, and lower fT4, HDL than controls., Conclusion: During their first admission, people with FEP, especially those with normal/low baseline BMI, showed a rapid and clinically significant weight increase, which was associated with exposure to antipsychotics, and with metabolic changes consistent with metabolic syndrome. These findings emphasize weight monitoring in FEP and suggest a greater need for caution when prescribing metabolically problematic antipsychotics to people with lower BMI., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to compare the effectiveness of semaglutide versus liraglutide for treating post-metabolic and bariatric surgery (MBS) weight recurrence., Methods: A retrospective analysis of 207 adults with post-MBS weight recurrence treated with semaglutide 1.0 mg weekly (n = 115) or liraglutide 3.0 mg daily (n = 92) at an academic center from January 1, 2015, through April 1, 2021, was conducted. The primary end point was percentage body weight change at 12 months of treatment with regimens containing semaglutide or liraglutide., Results: The mean sample age was 55.2 years; mean BMI was 40.4 kg/m 2 ; 89.9% were female; and 50% completed sleeve gastrectomy, 29% completed Roux-en-Y gastric bypass, and 21% completed adjustable gastric banding. Least-squares mean weight change at 12 months was -12.92% versus -8.77% in the semaglutide and liraglutide groups, respectively (p < 0.001). The adjusted odds ratios were 2.34 (95% CI: 1.28-4.29) for ≥10% weight loss and 2.55 (95% CI: 1.22-5.36) for ≥15% weight loss over 12 months in the semaglutide group versus liraglutide group, respectively. Weight-loss efficacy of semaglutide (vs. liraglutide) did not differ by subgroups explored, including age, sex, and MBS procedure., Conclusions: These results show that treatment regimens including semaglutide 1.0 mg weekly lead to superior weight loss compared with liraglutide 3.0 mg daily for treating post-MBS weight recurrence, regardless of procedure type or the magnitude of weight recurrence., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Background: Integrase inhibitor (INSTI) use has been associated with greater weight gain (WG) among people living with HIV (PLWH), but it is unclear how this effect compares in magnitude to traditional risk factors for WG. We assessed the population attributable fractions (PAFs) of modifiable lifestyle factors and INSTI regimens in PLWH who experienced a ≥5% WG over follow-up., Methods: In an observational cohort study from 2007 to 2019 at Modena HIV Metabolic Clinic, Italy, ART-experienced but INSTI-naive PLWH were grouped as INSTI-switchers vs non-INSTI. Groups were matched for sex, age, baseline BMI and follow-up duration. Significant WG was defined as an increase of ≥5% from 1st visit weight over follow-up. PAFs and 95% CIs were estimated to quantify the proportion of the outcome that could be avoided if the risk factors were not present., Results: 118 PLWH switched to INSTI and 163 remained on current ART. Of 281 PLWH (74.3% males), mean follow-up was 4.2 years, age 50.3 years, median time since HIV diagnosis 17.8 years, CD4 cell count 630 cells/µL at baseline. PAF for weight gain was the greatest for high BMI (45%, 95% CI: 27-59, p  < 0.001), followed by high CD4/CD8 ratio (41%, 21-57, p  < 0.001) and lower physical activity (32%, 95% CI 5-52, p  = 0.03). PAF was not significant for daily caloric intake (-1%, -9-13, p  = 0.45), smoking cessation during follow-up (5%, 0-12, p  = 0.10), INSTI switch (11%, -19-36; p  = 0.34)., Conclusions: WG in PLWH on ART is mostly influenced by pre-existing weight and low physical activity, rather than switch to INSTI.

Background and Hypothesis: Antipsychotic-induced weight gain is associated with alterations to the composition of the gut microbiota. The purpose of this study was to determine the effect of probiotics plus dietary fiber on antipsychotic-induced weight gain., Study Design: Two sequential, randomized clinical trials were conducted. In Study 1, 90 drug-naïve, first-episode schizophrenia patients were randomized to receive either olanzapine plus probiotics or olanzapine monotherapy for 12 weeks. In Study 2, 60 drug-naïve, first-episode schizophrenia patients were randomly assigned to receive either olanzapine plus probiotics and dietary fiber or olanzapine monotherapy for 12 weeks., Study Results: In Study 1, no significant differences in weight gain were observed between the two groups. The insulin resistance index (IRI) was lower in the olanzapine plus probiotics group compared with the olanzapine monotherapy group at week 12 (estimated mean difference, -0.65, [95% confidence interval (CI), -1.10 to -0.20]; p = .005). In Study 2, weight gain was lower in the probiotics plus dietary fiber group than in the olanzapine monotherapy group at week 12 (estimated mean difference -3.45 kg, [95% CI, -5.91 to -1.00]; p = .007). At week 12, IRI increased significantly in the olanzapine monotherapy group (mean, 1.74; standard deviation (SD) = 1.11, p < .001), but not in the olanzapine plus probiotics and dietary fiber group (mean 0.47, SD = 2.16, p = .35) with an estimated mean difference of -0.95 between the two groups [95% CI, -1.77 to -0.14]; p = .022)., Conclusions: These results provide support for the efficacy and safety of probiotics plus dietary fiber in attenuating antipsychotic-induced weight gain in drug-naïve, first-episode schizophrenia patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background and Purpose: Analogues of fibroblast growth factor 21 (FGF21) demonstrate diverse metabolic benefits in preclinical models of type 2 diabetes, dyslipidaemia and non-alcoholic steatohepatitis (NASH), but clinical responses with different analogues are inconsistent. Efruxifermin is an Fc-FGF21 fusion protein with prolonged half-life and enhanced receptor affinity compared with native human FGF21. Efruxifermin is in clinical trials for the treatment of non-alcoholic steatohepatitis., Experimental Approach: Efruxifermin was administered weekly to male and female Sprague Dawley rats for 4 or 26 weeks. Body and organ weights, macroscopic and microscopic pathology, clinical chemistry, blood cytology and serum and urine biomarkers were analysed to characterize the pharmacodynamics of efruxifermin and to investigate potential non-clinical toxicities following chronic administration of supra-pharmacological doses of efruxifermin., Key Results: Efruxifermin significantly reduced body weight gain after 4 and 26 weeks, despite increasing food intake. Changes in tissue pathology, clinical chemistry and serum biomarkers generally appeared to be associated with weight loss, except for a significant decrease in urine volume in both males and females without perturbed electrolyte balance. Markers of sympathetic activation, urinary corticosterone and ratio of adrenal-to-body weight were unchanged., Conclusion and Implications: Efruxifermin attenuated body weight gain, consistent with other FGF21 analogues. In contrast to at least one other FGF21 analogue, efruxifermin decreased rather than increased urine volume. The absence of an increase in sympathetic tone in rats mirrors the unchanged salivary cortisol and systemic blood pressure following efruxifermin treatment in humans., (© 2021 Akero Therapeutics, Inc. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

A part of atypical antipsychotics exert mood-stabilising effects via modulation of various monoamine receptors and intracellular signalling. Recent pharmacodynamic studies suggested that tripartite-synaptic transmission can be involved in pathophysiology of mood-disorders, schizophrenia, their associated cognitive impairments, and several adverse-reactions to atypical antipsychotics. Therefore, to explore mechanisms underlying antidepressive mood-stabilising and antipsychotic effects of lurasidone, we determined concentration-dependent effects of acute and subchronic lurasidone administrations on astroglial L-glutamate release, and expression of connexin43, ERK, AKT, adenosine monophosphate activated protein kinase (AMPK), 5-HT1A (5-HT1AR) and 5-HT7 (5-HT7R) receptors in cultured astrocytes using ultra-high-pressure liquid-chromatography with mass-spectrometry and capillary-immunoblotting systems. Therapeutically-relevant lurasidone concentration suppressed astroglial L-glutamate release through activated connexin43-containing hemichannel by decreasing connexin43 expression in plasma-membrane. Subchronic lurasidone administration downregulated 5-HT1AR and 5-HT7R in astroglial plasma-membrane concentration-dependently. Subchronic lurasidone administration attenuated ERK and AMPK signallings concentration-dependently without affecting AKT signalling. These results suggest that effects of subchronic lurasidone administration on astroglial L-glutamate release, 5-HT receptor, and intracellular signalling are similar to vortioxetine and different from mood-stabilising atypical antipsychotics, clozapine. Therefore, inhibitory effects of subchronic lurasidone administration on astroglial L-glutamate release through activated connexin43-containing hemichannel probably contribute to pathophysiology of antidepressive mood-stabilising effects of lurasidone. Furthermore, inhibitory effects of subchronic lurasidone administration on ERK and AMPK activities (without affecting AKT activity) induced by downregulation of 5-HT7R could result in clinical advantages of lurasidone, lower risk of weight gain., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

As a crucial metabolic intermediate, l-lactate is involved in redox balance, energy balance, and acid-base balance in organisms. Moderate exercise training transiently elevates plasma l-lactate levels and ameliorates obesity-associated type 2 diabetes. However, whether moderate l-lactate administration improves obesity-associated insulin resistance remains unclear. In this study, we defined 800 mg/kg/day as the dose of moderate l-lactate administration. In mice fed with a high-fat diet (HFD), moderate l-lactate administration for 12 weeks was shown to alleviate weight gain, fat accumulation, and insulin resistance. Along with the phenotype alterations, white adipose tissue thermogenesis was also found to be elevated in HFD-fed mice. Meanwhile, moderate l-lactate administration suppressed the infiltration and proinflammatory M1 polarization of adipose tissue macrophages (ATMs) in HFD-fed mice. Furthermore, l-lactate treatment suppressed the lipopolysaccharide-induced M1 polarization of bone marrow-derived macrophages (BMDMs). l-lactate can bind to the surface receptor GPR132, which typically drives the downstream cAMP-PKA signaling. As a nutrient sensor, AMP-activated protein kinase (AMPK) critically controls macrophage inflammatory signaling and phenotype. Thus, utilizing inhibitors of the kinases PKA and AMPK as well as siRNA against GPR132, we demonstrated that GPR132-PKA-AMPKα1 signaling mediated the suppression caused by l-lactate treatment on BMDM M1 polarization. Finally, l-lactate addition remarkably resisted the impairment of lipopolysaccharide-treated BMDM conditional media on adipocyte insulin sensitivity. In summary, moderate l-lactate administration suppresses ATM proinflammatory M1 polarization through activation of the GPR132-PKA-AMPKα1 signaling pathway to improve insulin resistance in HFD-fed mice, suggesting a new therapeutic and interventional approach to obesity-associated type 2 diabetes., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: People with severe mental illnesses (SMI) such as schizophrenia die on average 15 to 20 years earlier than everyone else. Two thirds of these deaths are from preventable physical illnesses such as hypertension, cardiovascular disease, and diabetes, which are worsened by weight gain. Antipsychotics are associated with significant weight gain. In REalist Synthesis Of non-pharmacologicaL interVEntions (RESOLVE), a realist synthesis, combining primary and secondary data, will be used to understand and explain how, why, for whom, and in what contexts non-pharmacological interventions can help service users to manage antipsychotic-induced weight gain., Methods: A five-step approach will be used to develop guidance: 1. Developing the initial programme theory An initial (candidate) programme theory, which sets out how and why outcomes occur within an intervention, will be developed. 2. Developing the search The initial programme theory will be refined using academic and grey literature. The proposed initial sampling frame are as follows: Context: people living with SMI, taking antipsychotics, different types of SMI., Intervention: non-pharmacological interventions., Mechanisms: triggered by the intervention. Outcomes e.g. weight, metabolic adverse events, quality of life, adherence, burden, economic. Searching for relevant documents will continue until sufficient data is found to conclude that the refined programme theory is coherent and plausible. Lived experience (service users) and stakeholder (practitioners) groups will provide feedback. 3. Selection, appraisal and data extraction Documents will be screened against inclusion and exclusion criteria. The text extracted from these documents will be coded as contexts, mechanisms and their relationships to outcomes. 4. Primary data collection Realist interviews with up to 30 service users and informal carers, and 20 practitioners will gather data to support, refute or refine the programme theory. 5. Data analysis A realist logic of analysis will be used to develop and refine the programme theory from secondary and primary data. The analysis will aim to identify practical intervention strategies to change contexts so that key mechanisms are triggered to produce desired outcomes. Guidance will be produced based on these strategies., Discussion: This realist synthesis aims to develop guidance for service users and practitioners on the most appropriate interventional strategies to manage and limit antipsychotic weight gain., Systematic Review Registration: PROSPERO: CRD42021268697., (© 2022. The Author(s).)

Hibiscus sabdariffa extract (HSE) and Syzygium cumini extract (SCE) have been used in traditional medicine due to their hypoglycemic, antidiabetic, anti-obesity and antioxidant activities. This study aimed to evaluate the anti-obesity effects of these extracts, as well as to evaluate their toxicities. The phytochemical profiles were obtained by HPLC-DAD-ESI-MS/MS analyses. Pharmacological screening, motor activity, motor coordination and acute toxicity were evaluated by administering HSE or SCE (oral or intraperitoneal routes) at different doses to mice. The anti-obesity effects were examined by assessing the decrease in food intake and body weight loss in Wistar albino rats and by gastrointestinal transit in Swiss albino mice. Sibutramine was used as the positive control. Both extracts showed no toxic effects. At the end of 7 days of treatment, we observed that SCE and HSE reduced the weight gain and food intake of the treated rats in relation to the controls. Sub-chronic treatment revealed that HSE, SCE and sibutramine had the best effect 7 and 14 days after starting treatment. After 28 days, the SCE group showed less weight gain and reduced food consumption compared to the HSE group and controls. In addition, intestinal transit was increased in the HSE group, which is probably due to the high fiber content of the extract and may explain its anti-obesity properties. Myricetin glycosides were found in high levels in SCE and low levels in HSE, which may be the main compounds associated with the anti-obesity effect found in SCE. It is not possible to suggest an effective dose without conducting a preclinical toxicology study. We recommend clinical studies that evaluate the efficacy and safety, as well as the effect of discontinuing the extracts.

Obesity has been reported to be associated with gut microbiome dysbiosis. seabuckthorn fruits have traditionally been used in Tibetan foods and medicines for thousands of years. Seabuckthorn polysaccharide (SP) is one of the main functional components in seabuckthorn fruits. However, the effects of SP on a high-fat diet (HFD)-induced obesity have not yet been elucidated. The purpose of this study is to explore the amelioration effect of SP on obesity induced by HFD and to reveal its mechanism of gut microbiota and its metabolites. Results showed that 12-week SP (0.1%, w/w) dietary supplementation could significantly reduce body weight gain, serum lipid level and liver triglycerides level in obese mice. Notably, the SP treatment elevated p-AMPKα and PPARα proteins expression stimulated the phosphorylation of ACC1 and inhibited the protein expression of FAS, PPARγ, and CD36 in the mice liver. Further, SP also reorganized the gut microbiome by up-regulating the proportion of Muribaculaceae&#95;unclassified , Bifidobacterium , Rikenellaceae&#95;RC9&#95;gut&#95;group , Alistipes , and Bacteroides , and down-regulating the abundance of Lactobacillus , Firmicutes&#95;unclassified, Dubosiella Bilophila , and Streptococcus in HFD-induced obese mice. Moreover, the production of microbial metabolites short-chain fatty acids (SCFAs) in feces has also increased. In addition, correlation analysis results showed that obesity-ameliorating effects of SP were highly associated with levels of SCFAs in feces. Therefore, the regulation of SP on liver lipid metabolism may be due to the variation of the gut microbiome and raised production of SCFAs. These results indicate that SP could play the part of a potential nutraceutical for ameliorating obesity through regulation of the gut-liver axis.

Pyrrosia lingua (Thunb.) Farw is a common plant that has been widely used as a traditional herbal medicine in China and Korea to treat patients suffering from pain, vaginal bleeding and urolithiasis. However, the pharmacological effects of P. lingua on bone remain unknown. We investigated the anti-osteoporotic effects of an ethanolic extract of P. lingua (EEPL). We found that EEPL suppressed osteoclast differentiation by directly acting on osteoclast precursor cells. EEPL suppressed the expression of receptor activator of nuclear factor-κB ligand (RANKL)-induced nuclear factor of activated T cells 1, a major transcription factor for osteoclastogenesis, by inhibiting RANKL-induced expression of aryl hydrocarbon receptor/c-Fos, and activation of nuclear factor-κB and mitogen-activated protein kinases. Moreover, administration of EEPL inhibited trabecular bone loss and weight gain in ovariectomized mice. Furthermore, we identified phytochemicals in EEPL that are known to exert anti-osteoclastogenic or anti-osteoporotic effects using ultra-high-performance liquid chromatography-tandem mass-spectrometry analysis. Overall, the results of this study suggest that EEPL is effective therapeutic candidate that can be used to prevent or treat postmenopausal osteoporosis., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Tribulus terrestris saponins (TTS) have been longley used as an overall tonic and recent studies showed they influence inflammatory conditions. We examined the ameliorative effect of a commercial formula of a saponin-rich extract of TT in a model of dietary obesity in female rats focusing on their ability to control the inflammatory burden, insulin resistance (IR), adipokine expression and the related reproductive system pathologies. Female rats were fed with high fat diet (HFD) for 14 weeks to launch diet-induced obesity; they were assigned as: the obese control female rats (OFR) which received no treatment and TTS (5 and 10 mg/kg/day) treated rats; they were compared to a normal rat group. We determined the IR index, serum/tissue inflammatory cytokines, and adipose tissue adipokine expression and examined the secondary ovarian pathologies. Body weight gain, serum triglycerides and IR (>5-fold) in the OFR group were greater than the normal group; TTS lessened these parameters compared with the OFR group. TTS, at 10 mg/kg dose, ameliorated mRNA expression of leptin and visfatin genes in addition to serum inflammatory cytokine levels. Moreover, TTS corrected the hyperprolactinemia and other hormonal disturbances and ameliorated the ovarian pathologies. This study highlighted that the anti-inflammatory properties of TTS helped in alleviation of IR and body weight gain in OFR. Upon correction of obesity manifestations, the gonadal hormone dysregulations and ovarian pathologies were subsequently ameliorated. We can consider TTS as a promising candidate that may alleviate the inflammatory burden, IR and adipokine expression in obesity and hence prevent the secondary gonadal complications in female subjects if appropriate clinical studies are available., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Mirtazapine (MIRT) is a multi-target antidepressant used in treatment of severe depression with promising efficacy, but also with important side effects, mainly sedation and weight gain. Thus, the present study aimed to test the effects of the neuroprotective antioxidant lipoic acid (ALA) in the reversal of weight and metabolic changes induced by MIRT in corticosterone-induced depression model in mice, as well as proposed mechanisms for their association antidepressant and pro-cognitive effects. To do these male Swiss mice received Tween 80 (control), corticosterone (CORT 20 mg / kg), MIRT (3 mg / kg) and ALA (100 or 200 mg / kg), alone or associated for 21 days. After this, the animals were subjected to behavioral tests for affective and cognitive domains. Daily weight changes, blood cholesterol fractions and corticosterone were measured. Also, hippocampus (HC) protein expression of the serotonin transporter (SERT), synaptophysin, protein kinase B-Akt (total and phosphorylated) and the cytokines IL-4 and IL-6 were investigated. CORT induced a marked depression-like behavior, memory deficits, metabolic changes (total cholesterol and LDL) and increased serum corticosterone. Also, CORT increased SERT expression in the HC. MIRT alone or combined with ALA sustained its antidepressant-like effect, as well as reversed CORT-induced impairment in spatial recognition memory. Additionally, the association MIRT+ALA200 reversed the weight gain induced by the former antidepressant, as well as reduced serum corticosterone levels and SERT expression in the HC. ALA alone induced significant weight loss and reduced total cholesterol and HDL fraction. Our findings provide promising evidence about the ALA potential to prevent metabolic and weight changes associated to MIRT, without impair its antidepressant and pro-cognition actions. Therefore, ALA+MIRT combination could represent a new therapeutic strategy for treating depression with less side effects., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: High carbohydrate diet and carbonated soda consumption have individually been associated with metabolic dysfunction, with links to glucose and insulin homeostasis, affecting metabolic variables associated with feeding, satiety and adiposity. Our objective is to determine the combined effect of a high carbohydrate and carbonated soda diet on metabolic variables in male and female Wistar rats., Materials and Methods: Thirty-two female and male weanlings were equally divided into four dietary groups; Control, Soda, High Carbohydrate diet (HCD), and High Carbohydrate diet/Soda (HCD/Soda), and fed ad libitum for fourteen weeks. Bodyweight, thoracic circumference, abdominal circumference and glucose was determined; Insulin, leptin, adiponectin, Tumor Necrotic Factor (TNF)-α, Interleukin (IL)-6 and lipid profile were assayed and used to determine the metabolic effects., Key Findings: Soda and HCD/Soda had increased body weight in male rats, while HCD-fed rats were reduced compared to respective controls. Abdominal circumference, total cholesterol and reduced HDL of Soda were elevated in both sexes. Although HCD/Soda groups had elevated abdominal circumference in both sexes, total cholesterol and reduced high-density lipoprotein (HDL) were both reduced in females. Insulin and malondialdehyde (MDA) concentrations in Soda-fed rats was significantly reduced, however, MDA was elevated in both sexes in HCD and HCD/Soda fed rats. Female HCD and HCD/Soda groups had a significant increase in glutathione (GSH) concentration and a significant reduction in catalase. TNF-α was increased in both Soda and HCD/Soda groups., Significance: The results of this study suggest that HCD and Soda consumption results in alteration in phenotype and variables impacting metabolism., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Interactions between obesity and opioid use are poorly understood. The objective of this study was to determine whether phenotypic differences in diet-induced weight gain altered morphine withdrawal responses. Male and female C57BL/6J mice were characterized as obese prone (OP) or obese resistant (OR) based on median split in body weights following exposure to high-fat diet (45% fat). After classification into OP or OR, all mice were fed a low-fat diet (10% fat) for the remainder of the study (≥5 weeks) to remain weight matched. Mice were treated with a 7-day escalating dosing scheme of morphine (20-100 mg/kg; IP) or saline and underwent a spontaneous withdrawal. Morphine-induced weight loss was restored by withdrawal day 7. On withdrawal day 8, male OP demonstrated less total time mobile in the open field test (OFT). In females, OR-morphine traveled less distance than OR-saline, and OR-morphine spent less time mobile compared with all other groups in the OFT. Female OP also increased time spent in the center of the apparatus, regardless of treatment. On withdrawal day 8, relative gene expression was measured by qPCR. For males, expression of dopamine beta-hydroxylase (dbh), alpha-adrenergic receptor 2 a (adra2a), and orexin receptor 1 (orx1) were increased in the locus coeruleus (LC) region of OP mice, regardless of treatment. In comparison, in females, dbh and adra2a were decreased in the LC region of OP mice, regardless of treatment. Also, in the LC region of females, OP-morphine had lower expression of alpha-adrenergic receptor 1 a (adra1a) than OR-morphine and OP-saline. In the hypothalamic paraventricular nucleus (PVN) of females, adra2a was increased in OP-morphine compared with OP-saline and OR-morphine. Our findings suggest morphine withdrawal responses and regional expression of noradrenergic-related genes are differentially influenced by weight gain propensity., (Copyright © 2022 Elsevier Inc. All rights reserved.)