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Purpose To assess adherence to the US Liver Imaging Reporting and Data System (LI-RADS) recommendations for hepatocellular carcinoma (HCC) surveillance and associated patient-level factors in a vulnerable, diverse patient sample. Materials and Methods The radiology report database was queried retrospectively for patients who underwent US LI-RADS-based surveillance examinations at a single institution between June 1, 2020, and February 28, 2021. Initial US and follow-up liver imaging were included. Sociodemographic and clinical data were captured from electronic medical records. Adherence to radiologist recommendation was defined as imaging (US, CT, or MRI) follow-up in 5-7 months for US-1, imaging follow-up in 3-6 months for US-2, and CT or MRI follow-up in 2 months for US-3. Descriptive analysis and multivariable modeling that adjusted for age, sex, race, and time since COVID-19 pandemic onset were performed. Results Among 936 patients, the mean age was 59.1 years; 531 patients (56.7%) were male and 544 (58.1%) were Asian or Pacific Islander, 91 (9.7%) were Black, 129 (13.8%) were Hispanic, 147 (15.7%) were White, and 25 (2.7%) self-reported as other race. The overall adherence rate was 38.8% (95% CI: 35.7, 41.9). The most common liver disease etiology was hepatitis B (60.6% [657 of 936 patients]); 19.7% of patients (183 of 936) had current or past substance use disorder, and 44.8% (416 of 936) smoked. At adjusted multivariable analysis, older age (odds ratio [OR], 1.20; P = .02), male sex (OR, 1.62; P = .003), hepatology clinic attendance (OR, 3.81; P < .001), and recent prior US examination (OR, 2.44; P < .001) were associated with full adherence, while current smoking (OR, 0.39; P < .001) was negatively associated. Conclusion Adherence to HCC imaging surveillance was suboptimal, despite US LI-RADS implementation. Keywords: Liver, Ultrasound, Screening, Abdomen/GI, Cirrhosis, Metabolic Disorders, Socioeconomic Issues Supplemental material is available for this article. © RSNA, 2024.

Background: This study aimed to investigate the clinical and molecular genetic characteristics of ten children with ornithine carbamoyltransferase deficiency (OTCD) in southeastern China, as well as the correlation between the genotype and phenotype of OTCD. Methods: A retrospective analysis was performed on the clinical manifestations, laboratory testing, and genetic test findings of ten children with OTCD admitted between August 2015 and October 2021 at Quanzhou Maternity and Children's Hospital of Fujian Province in China. Results: Five boys presented with early-onset symptoms, including poor appetite, drowsiness, groaning, seizures, and liver failure. In contrast, five patients (one boy and four girls) had late-onset gastrointestinal symptoms as the primary clinical manifestation, all presenting with hepatic impairment, and four with hepatic failure.Nine distinct variants of the OTC gene were identified, including two novel mutations: c.1033del(p.Y345Tfs*50) and c.167T > A(p.M56K). Of seven patients who died, five had early-onset disease despite active treatment. Three patients survived, and two of them underwent liver transplantation. Conclusions: The clinical manifestations of OTCD lack specificity. However, elevated blood ammonia levels serve as a crucial diagnostic clue for OTCD. Genetic testing aids in more accurate diagnosis and prognosis assessment by clinicians. In addition, we identified two novel pathogenic variants and expand the mutational spectrum of the gene OTC, which may contribute to a better understanding of the clinical and genetic characteristics of OTCD patients. [ABSTRACT FROM AUTHOR]

Energy metabolism disorders leading to tissue destruction are major causes of osteoporosis. While efficacious, bone repair strategies that modulate energy metabolism pose considerable challenges. Herein, an energetic calcium phosphate nanominerals (ECPN) is developed using polyphosphate as an energy source for osteoporosis treatment. ECPN promotes adenosine triphosphate (ATP) production in the physiological environment, providing energy to attain metabolic homeostasis. It significantly enhances rBMSCs’ autophagy capacity by activating the AMPK‐related pathway, promoting osteogenic differentiation, and rebuilding the bone regeneration microenvironment. ECPN's unique nanostructure can fully mineralize collagen fibers, enhancing the bone matrix's mechanical properties. In vivo, ECPN rapidly infiltrates osteoporotic bones, fills defects, mineralizes the matrix, and promotes new‐bone formation. The repaired bone exhibits mechanical properties comparable to those of normal bones. ECPN balances the time‐sensitive need for immediate bone matrix mineralization and long‐term construction of an osteogenic microenvironment during osteoporosis treatment. The potential of this metabolic fuel for generating functional nanomaterials for tissue engineering has been underestimated in the past. The concept of an energetic nanomineral for tissue regeneration may elicit new trends in tissue engineering. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS), as a set of medical conditions including hyperglycemia, hypertension, abdominal obesity, and dyslipidemia, represents a highly prevalent disease cluster worldwide. The individual components of MetS together increase the risk of MetS-related disorders. Recent research has demonstrated that bone, as an endocrine organ, releases several systemic cytokines (osteokines), including fibroblast growth factor 23 (FGF23), lipocalin 2 (LCN2), and sclerostin (SCL). This review not only summarizes current knowledge about MetS, osteokines and the most common MetS-related diseases with a detrimental impact on bone quality (type 2 diabetes mellitus: T2DM; cardiovascular diseases: CVDs; osteoporosis: OP), but also provides new interpretations of the relationships between osteokines and individual components of MetS, as well as between osteokines and MetS-related diseases mentioned above. In this context, particular emphasis was given on available clinical studies. According to the latest knowledge, FGF23 may become a useful biomarker for obesity, T2DM, and CVDs, as FGF23 levels were increased in patients suffering from these diseases. LCN2 could serve as an indicator of obesity, dyslipidemia, T2DM, and CVDs. The levels of LCN2 positively correlated with obesity indicators, triglycerides, and negatively correlated with high-density lipoprotein (HDL) cholesterol. Furthermore, subjects with T2DM and CVDs had higher LCN2 levels. SCL may act as a potential biomarker predicting the incidence of MetS including all its components, T2DM, CVDs, and OP. Elevated SCL levels were noted in individuals with T2DM, CVDs and reduced in patients with OP. The aforementioned bone-derived cytokines have the potential to serve as promising predictors and prospective treatment targets for MetS and MetS-related diseases negatively affecting bone quality. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) has emerged as a promising biomarker for assessing inflammation and lipid dysregulation. Increasing evidence indicates that these metabolic disturbances play a crucial role in the development of metabolic dysfunction-associated steatotic liver disease(MASLD). This study aims to investigate the association between NHR, MASLD, and liver fibrosis. Methods: This cross-sectional study analyzed data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES). Weighted multivariate logistic regression models were used to investigate the association between NHR and both MASLD and liver fibrosis. Smoothed curve fitting and threshold effect analysis were performed to detect potential nonlinear relationships. Subgroup analyses were conducted to assess the consistency of these associations across different groups. Results: The study involved 4,761 participants. We observed a significant positive association between NHR and MASLD (OR = 1.20, 95% CI: 1.09–1.31). However, there was no significant association between NHR and liver fibrosis (OR = 1.01; 95% CI: 0.94–1.09). The analysis of smoothed curve fitting and threshold effect revealed an inverted U-shaped relationship between NHR and MASLD, with a turning point at 5.63. Conclusion: Our findings indicate a positive correlation between elevated NHR levels and MASLD prevalence. However, we did not observe a significant association between NHR and liver fibrosis prevalence. Further prospective research is needed to validate these findings in a longitudinal setting. [ABSTRACT FROM AUTHOR]

Background: In recent years, the incidence of Endometrial cancer (EC) has been on the rise due to high-fat, high-calorie diets and low-exercise lifestyles. However, the relationships between metabolic disorders and the progression of EC remain uncertain. The purpose of our study was to explore the potential association between obesity, hypertension, hyperglycemia and clinicopathologic characteristics in EC patients. Methods: In categorical variables, Chi-square tests were used to calculate P values. Univariate logistic regression and multivariate logistic regression were used to identify the risk factors of myometrial invasion>1/2 and lymph node metastasis. Overall survival (OS) was estimated using the Kaplan-Meier method. Results: The study included 406 individuals with EC, 62.6% had type I and 37.4% had type II. Hypertension was seen in 132 (32.5%), hyperglycemia in 75 (18.5%), and overweight or obesity in 217 (53.4%). Hypertension, hyperglycemia, and obesity are strongly associated with the clinicopathologic features of EC. Multivariate logistic regression revealed that hyperglycemia (OR=2.439,95% CI: 1.025-5.804, P = 0.044) was a risk factor for myometrial invasion depth >1/2 in patients with type I EC, and hypertension (OR=32.124,95% CI: 3.287-313.992, P = 0.003) was a risk factor for lymph node metastasis in patients with type I EC. Survival analysis found that hyperglycemia (P < 0.001) and hypertension (P = 0.002) were associated with OS in type I EC. Neither hyperglycemia, hypertension, nor obesity were associated with the prognosis in type II EC. Conclusion: Hyperglycemia was a risk factor for myometrial invasion depth >1/2 in patients with type I EC and hypertension was a risk factor for lymph node metastasis in patients with type I EC. Hypertension and hyperglycemia were associated with poor prognosis in patients with type I EC. [ABSTRACT FROM AUTHOR]

Background: β-thalassemia (β-TH) is a hereditary hemolytic anemia that results in deficient hemoglobin (Hb) synthesis. It is characterized by ineffective erythropoiesis, anemia, splenomegaly, and systemic iron overload. Exploration new potential biomarkers and drug candidates is important to facilitate the prevention and treatment of β-TH. Methods: We applied quasi-targeted metabolomics between wild type (Wt) and heterozygous β-TH mice (Th3/+), a model of non-transfusion-dependent β-TH intermedia, in plasma and peripheral blood (PB) cells. Futher data was deeply mined by Kyoto Encyclopedia of Genomes (KEGG) and machine algorithms methods. Results: Using KEGG enrichment analysis, we found that taurine and hypotaurine metabolism disorders in plasma and alanine, aspartate and glutamate metabolism disorders in PB cells. After systematically anatomize the metabolites by machine algorithms, we confirmed that alpha-muricholic acidUP and N-acetyl-DL-phenylalanineUP in plasma and Dl-3-hydroxynorvalineUP, O-acetyl-L-serineUP, H-abu-OHUP, S-(Methyl) glutathioneUP, sepiapterinDOWN, and imidazoleacetic acidDOWN in PB cells play key roles in predicting the occurrence of β-TH. Furthermore, Sepiapterin, Imidazoleacetic acid, Methyl alpha-Dglucopyranoside and alpha-ketoglutaric acid have a good binding capacity to hemoglobin E through molecular docking and are considered to be potential drug candidates for β-TH. Conclusion: Those results may help in identify useful molecular targets in the diagnosis and treatment of β-TH and lays a strong foundation for further research. [ABSTRACT FROM AUTHOR]

Type 1 Diabetes (T1D) is a chronic metabolic disease resulting from insulin deficiency due to autoimmune loss of pancreatic β cells. In addition to β cell destruction, it is now accepted that β cell stress and dysfunction, such as senescence, plays a crucial role in the development of the disease. Accumulation of senescent β cells occurs during development of T1D in humans and contributes to the progression of T1D in the nonobese diabetic (NOD) mouse model. Senescent β cells are thought to exacerbate the inflammatory response within the islets by production and secretion of senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) from β cells have been shown to carry protein and microRNAs (miRNAs), influencing cellular signaling and may contribute to the development of T1D but it remains to be addressed how senescence impacts β cell EV cargo. In this minireview, we discuss emerging evidence that EV cargo proteins and miRNAs associated with senescence could contribute to the development of T1D and could suggest potential biomarkers and therapeutic targets for the regulation of SASP and elimination of senescent β cells in T1D. Future investigation exploring the intricate relationship between β cell senescence, EVs and miRNAs could pave the way for the development of novel diagnostic techniques and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Several metabolites have been shown to have independent and at times unexpected biological effects outside of their metabolic pathways. These include succinate, lactate, fumarate, and 2-hydroxyglutarate. 2-Hydroxybutyrate (2HB) is a byproduct of endogenous cysteine synthesis, produced during periods of cellular stress. 2HB rises acutely after exercise; it also rises during infection and is also chronically increased in a number of metabolic disorders. We show here that 2HB inhibits branched-chain aminotransferase enzymes, which in turn triggers a SIRT4-dependent shift in the compartmental abundance of protein ADP-ribosylation. The 2HB-induced decrease in nuclear protein ADP-ribosylation leads to a C/EBPβ-mediated transcriptional response in the branched-chain amino acid degradation pathway. This response to 2HB exposure leads to an improved oxidative capacity in vitro. We found that repeated injection with 2HB can replicate the improvement to oxidative capacity that occurs following exercise training. Together, we show that 2-HB regulates fundamental aspects of skeletal muscle metabolism. [ABSTRACT FROM AUTHOR]

Testosterone (T) and 17β-estradiol (E2 ) are produced in male and female humans and are potent metabolic regulators in both sexes. When E2 and T production stops or decreases during aging, metabolic dysfunction develops and promotes degenerative metabolic and vascular disease. Here, we discuss the shared benefits afforded by E2 and T for metabolic function human females and males. In females, E2 is central to bone and vascular health, subcutaneous adipose tissue distribution, skeletal muscle insulin sensitivity, antiinflammatory immune function, and mitochondrial health. However, T also plays a role in female skeletal, vascular, and metabolic health. In males, T’s conversion to E2 is fundamental to bone and vascular health, as well as prevention of excess visceral adiposity and the promotion of insulin sensitivity via activation of the estrogen receptors. However, T and its metabolite dihydrotestosterone also prevent excess visceral adiposity and promote skeletal muscle growth and insulin sensitivity via activation of the androgen receptor. In conclusion, T and E2 are produced in both sexes at sex-specific concentrations and provide similar and potent metabolic benefits. Optimizing levels of both hormones may be beneficial to protect patients from cardiometabolic disease and frailty during aging, which requires further study. [ABSTRACT FROM AUTHOR]

Background: Carboxylesterase 1(CES1) is expressed mainly in the liver and adipose tissue and is highly hypothesized to play an essential role in metabolism. Our study aimed to investigate the association between CES1 and metabolic syndrome (MetS) and metabolic dysfunction associated steatotic liver disease (MASLD) in children with obesity in China. Methods: This study included 72 children with obesity aged 6-13years (including 25(35%) diagnosed as MetS and 36(50%) diagnosed as MASLD). All subjects were measured in anthropometry, serum level of biochemical parameters related to obesity, circumstance levels of insulin-like growth factor1, adipokines (adiponectin, leptin and growth differentiation factor 15) and CES1. Results: Higher serum CES1 level were found in the MetS group (P = 0.004) and the MASLD group (P < 0.001) of children with obesity. Serum CES1 levels were positively correlated with alanine aminotransferase, aspartate aminotransferase, triglyceride, cholesterol, low-density lipoprotein cholesterol, GDF15, Leptin and negatively correlated with high-density lipoprotein cholesterol, adiponectin and IGF1. We also found a multivariable logistic regression analysis of MASLD and MetS predicted by CES1 significantly (MASLD P < 0.01, MetS P < 0.05). The combination of CES1, sex, age and BMI Z-score showed a sensitivity and specificity of 92.7% for the identification of MASLD and 78.6% for the identification of MetS. The cutoff for CES1 of MASLD is 56.30 ng/mL and of MetS is 97.79 ng/mL. Conclusions: CES1 is associated with an increasing risk of MetS and MASLD and can be established as a biomarker for metabolic syndrome and MASLD of children with obesity. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction associated fatty liver disease (MAFLD) is a common cause of liver disease in children and adolescents. The relationship between insulin resistance (IR) and MAFLD in children with short stature remains largely unknown. The present study was to investigate the relationship between the triglyceride–glucose (TyG) index and alanine aminotransferase (ALT) levels in children with short stature. A total of 1754 children with short stature were enrolled. Anthropometric, biochemical and hormonal indexes were collected through physical measurement examinations and laboratory tests. A nonlinear association was found between the TyG index and ALT. The inflection point of the curve was at a TyG index of 8.24. In multivariate piecewise linear regression, only when the TyG index was greater than 8.24 was there a significant positive association between the TyG index and ALT (β 5.75, 95% CI 3.30, 8.19; P < 0.001). However, when the TyG index was less than 8.24, there was no significant association between the TyG index and ALT (β −0.57, 95% CI −1.84, 0.71; P = 0.382). This study demonstrated a nonlinear relationship between TyG index and ALT in children with short stature. This finding suggests that a high TyG index is associated with elevated ALT in children with short stature. [ABSTRACT FROM AUTHOR]

Background: China has undergone a significant socioeconomic transformation over the past few decades due to the implementation of family planning policies. These societal changes have resulted in an increased susceptibility among females to developing cardiometabolic diseases (CMD). Unfortunately, studies investigating the correlation between family planning policies in China and the incidence of CMD remain scarce. Methods: Data from 1,226 females, aged 30 years or older with ≥ 1 live birth, undergoing routine physical examinations between January 2018 and December 2021 were collected, and they were grouped by number of live births 1, 2, and ≥ 3. A binary logistic regression model was employed to examine the association between the number of live births with CMD. Furthermore, the subgroup analysis was performed to elucidate the impact of the implementation of family planning policies with CMD. Results: Women with live births ≥ 3 tended to be older, had higher gravidities, a greater proportion of central obesity, general obesity, hypertension, and dyslipidemia (all P < 0.05). Across the three groups (live birth = 1, =2 and ≥ 3), the odds ratio (OR) with 95% CI for obesity were: 1.00, 3.32 (2.36–4.69), and 5.73 (3.79–8.68); for dyslipidemia were: 1.00, 1.75 (1.29–2.39), and 2.02 (1.38–2.94); and for CMD were: 1.00, 1.91 (1.44–2.54), and 2.15 (1.46–3.15), respectively (all P < 0.05). In addition, based on the different periods of the childbearing policy in China, a subgroup analysis (where age was divided into ≤ 45, 45–65, and ≥ 65 years old) found that each additional live birth increased the prevalence risk of obesity and CMD in the younger generations, while hypertension and dyslipidemia in the elder generation. Conclusions: Higher live births are positively associated with the prevalence of CMD among women in Southwest China. Moreover, giving birth after the implementation of the one-child policy tends to have a higher risk of developing CMD. [ABSTRACT FROM AUTHOR]

Background: The role of dietary fat quality in promotion of cardiovascular diseases is studies before. However, the results are inconsistent. Recently, cholesterol to saturated fatty acid index (CSI) is suggested as a novel indicator of the atherogenicity and thrombogenicity potential of a diet. However, due to limited number of studies, in the current cross-sectional study, we aimed to evaluate the role of CSI in metabolic and inflammatory response among obese individuals. Methods: In the current cross-sectional study 488 obese individuals aged 18–50 years old were involved in volunteer based invitation from outpatient obesity clinics. Subjects underwent anthropometric assays including weight, height, waist circumference (WC) and body composition and their fasting blood sample were obtained for biochemical assessments including blood sugar, serum lipids, hs-CRP and IL-6 concentrations by commercial kits. Physical activity was also assessed by short form of international physical activity questionnaire (IPAQ). Results: According to our results, being at the top tetile of CSI was associated with higher anthropometric indices including weight, height, WC, FFM, and basal metabolic rate (BMR) compared with those at the lowest tertile (P < 0.05). Similarly, those at the highest category of CSI had significantly higher levels of serum glucose and hs-CRP both in crude and adjusted models in ANCOVA and in multinomial logistic regression models (P < 0.05). Conclusion: In the current study, for the first time, we identified the possible triggering role of dietary cholesterol to saturated fat index in increasing serum glucose and hs-CRP levels. due to cross-sectional design of the current study, causal inference is impossible. Further studies will help for better scientific justification. [ABSTRACT FROM AUTHOR]

Background: Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins. Methods: The keywords "lipid droplets" and "metabolic diseases" were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like "lipid droplets", "lipid droplet-associated proteins", "fatty liver disease", "diabetes", "diabetic kidney disease", "obesity", "atherosclerosis", "hyperlipidemia", "natural drug monomers" and "natural compounds", the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized. Results: The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases. Conclusion: Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions The extent to which metabolic syndrome (MetS) severity influences subclinical myocardial remodelling, heart failure (HF) incidence and subtypes, remains unclear. We assessed the association of MetS with incident HF (including ejection fraction subtypes) among Black individuals.We included 4069 Jackson Heart Study participants (mean age 54.4 years, 63.8% women, 37.2% with MetS) without HF. We categorized participants based on MetS status and MetS severity scores (based on waist circumference [MetS‐Z‐WC] and body mass index [MetS‐Z‐BMI]). We assessed the associations of MetS indices with echocardiographic parameters, biomarkers of myocardial damage (high‐sensitivity cardiac troponin I [hs‐cTnI] and B‐type natriuretic peptide [BNP]) and incident HF hospitalizations including HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). MetS severity was associated with subclinical cardiac remodelling (assessed by echocardiographic measures and biomarkers of myocardial damage). Over a median of 12 years, 319 participants developed HF (157 HFpEF, 149 HFrEF and 13 HF of unknown type). MetS was associated with a twofold greater risk of HF (hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.64–2.61). Compared to the lowest quartile (Q1) of MetS‐Z‐WC, the highest quartile (Q4) conferred a higher risk of HF (HR 2.35, 95% CI 1.67–3.30), with a stronger association for HFpEF (Q4 vs. Q1: HR 4.94, 95% CI 2.67–9.14) vs. HFrEF (HR 1.69, 95% CI 1.06–2.70).Metabolic syndrome severity was associated with both HF subtypes among Black individuals, highlighting the importance of optimal metabolic health for preventing HF. [ABSTRACT FROM AUTHOR]

Background: Infertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin level on female reproduction remain unclear. Methods: Transgenic pigs overexpressing leptin (♀) were produced by backcrossing and screened for leptin overexpression. The growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single-nucleus RNA sequencing (snRNA-seq) of the leptin-overexpressing pigs and wild-type group were evaluated. Results: Transgenic pigs overexpressing leptin (♀) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested a late onset of puberty (330 ± 54.3 vs. 155 ± 14.7 days), irregular estrous behavior characterized by increased inter-estrous interval (29.2 ± 0 vs. 21.3 ± 0.7 days), and more number of matings until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum cholesterol esters along with steroidogenic markers (StAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells in the ovaries. Moreover, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Furthermore, snRNA-seq reflected that leptin overexpression triggered immune response, suppressed follicle development and luteinization, resulting in metabolic dysfunction and hormone imbalance in the ovary. Conclusions: Low body weight in leptin overexpressing pigs adversely affects the reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, an increased immune response, and altered ovarian functions. This study provides a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressing female pigs. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) and obesity are prevalent metabolic disorders in the Indian population, often linked to lifestyle changes leading to metabolic alterations. Elevated levels of circulating saccharides contribute to various metabolic disturbances, including T2DM and associated complications such as renal and retinal dysfunction. This study aimed to identify individuals at risk of T2DM through lipid profiling in Bhiwadi, Rajasthan. A total of 800 participants were enrolled, and parameters including lipid profiling levels (HDL, Cholesterol) were assessed. Among the participants, 400 males and 400 females exhibited lipid profiles indicative of T2DM risk. These findings underscore the significance of lipid profiling in identifying individuals at risk of T2DM and obesity-related complications. Lifestyle modifications and targeted interventions are crucial to mitigate the growing burden of these metabolic disorders, particularly in regions like Bhiwadi, Rajasthan, India. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel form of programmed cell death caused by damage to lipid membranes due to the accumulation of lipid peroxides in response to various stimuli, such as high levels of iron, oxidative stress, metabolic disturbance, etc. Sugar, lipid, amino acid, and iron metabolism are crucial in regulating ferroptosis. The solute carrier transporters (SLCs) family, known as the "metabolic gating" of cells, is responsible for transporting intracellular nutrients and metabolites. Recent studies have highlighted the significant role of SLCs family members in ferroptosis by controlling the transport of various nutrients. Here, we summarized the function and mechanism of SLCs in ferroptosis regulated by ion, metabolic control of nutrients, and multiple signaling pathways, with a focus on SLC–related transporters that primarily transport five significant components: glucose, amino acid, lipid, trace metal ion, and other ion. Furthermore, the potential clinical applications of targeting SLCs with ferroptosis inducers for various diseases, including tumors, are discussed. Overall, this paper delves into the novel roles of the SLCs family in ferroptosis, aiming to enhance our understanding of the regulatory mechanisms of ferroptosis and identify new therapeutic targets for clinical applications. [ABSTRACT FROM AUTHOR]

Background: Spontaneous preterm birth (sPTB) is a global disease that is a leading cause of death in neonates and children younger than 5 years of age. However, the etiology of sPTB remains poorly understood. Recent evidence has shown a strong association between metabolic disorders and sPTB. To determine the metabolic alterations in sPTB patients, we used various bioinformatics methods to analyze the abnormal changes in metabolic pathways in the preterm placenta via existing datasets. Methods: In this study, we integrated two datasets (GSE203507 and GSE174415) from the NCBI GEO database for the following analysis. We utilized the "Deseq2" R package and WGCNA for differentially expressed genes (DEGs) analysis; the identified DEGs were subsequently compared with metabolism-related genes. To identify the altered metabolism-related pathways and hub genes in sPTB patients, we performed multiple functional enrichment analysis and applied three machine learning algorithms, LASSO, SVM-RFE, and RF, with the hub genes that were verified by immunohistochemistry. Additionally, we conducted singlesample gene set enrichment analysis to assess immune infiltration in the placenta. Results: We identified 228 sPTB-related DEGs that were enriched in pathways such as arachidonic acid and glutathione metabolism. A total of 3 metabolismrelated hub genes, namely, ANPEP, CKMT1B, and PLA2G4A, were identified and validated in external datasets and experiments. A nomogram model was developed and evaluated with 3 hub genes; the model could reliably distinguish sPTB patients and term labor patients with an area under the curve (AUC) > 0.75 for both the training and validation sets. Immune infiltration analysis revealed immune dysregulation in sPTB patients. Conclusion: Three potential hub genes that influence the occurrence of sPTB through shadow participation in placental metabolism were identified; these results provide a new perspective for the development and targeting of treatments for sPTB. [ABSTRACT FROM AUTHOR]

Objective: Craniopharyngiomas (CPG) have complex treatment challenges due to their proximity to vital structures, surgical and radiotherapeutic complexities, and the tendency for recurrence. The aim of this study was to identify the prevalence of endocrine and metabolic comorbidities observed during initial diagnosis and long-term follow-up in a nationwide cohort of pediatric CPG patients. A further aim was to highlight the difficulties associated with CPG management. Methods: Sixteen centers entered CPG patients into the ÇEDD NET data system. The clinical and laboratory characteristics at presentation, administered treatments, accompanying endocrine, metabolic, and other system involvements, and the patient's follow-up features were evaluated. Results: Of the 152 evaluated patients, 64 (42.1%) were female. At presentation, the mean age was 9.1±3.67, ranging from 1.46 to 16.92, years. The most common complaints at presentation were headache (68.4%), vision problems (42%), short stature (15%), and nausea and vomiting (7%). The surgical procedures were gross total resection (GTR) in 97 (63.8%) and subtotal resection in 55 (36.2%). Radiotherapy (RT) was initiated in 11.8% of the patients. Histopathological examination reported 92% were adamantinamatous type and 8% were papillary type. Postoperatively, hormone abnormalities consisted of thyroid-stimulating hormone (92.1%), adrenocorticotropic hormone (81%), antidiuretic hormone (79%), growth hormone (65.1%), and gonadotropin (43.4%) deficiencies. Recombinant growth hormone treatment (rhGH) was initiated in 27 (17.8%). The study showed hesitancy among physicians regarding rhGH. The median survival without relapse was 2.2 years. Median (range) time of relapse was 1.82 (0.13-10.35) years. Relapse was related to longer followups and reduced GTR rates. The median follow-up time was 3.13 years. Among the last follow-up visits, the prevalence of obesity was 38%, but of these, 46.5% were already obese at diagnosis. However, 20% who were not obese at baseline became obese on follow-up. Permanent visual impairment was observed in 26 (17.1%), neurological deficits in 13 (8.5%) and diabetes mellitus in 5 (3.3%) patients. Conclusion: Recurrence was predominantly due to incomplete resection and the low rate of postoperative RT. Challenges emerged for multidisciplinary regular follow ups. It is suggested that early interventions, such as dietary restrictions and increased exercise to prevent obesity, be implemented. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is the most common metabolic disorder among women of reproductive age. Many factors are involved in the development of PCOS, among which genetic predisposition is probably the main contributor that is also influenced by lifestyle and environmental factors. This study aims to determine the prevalence of PCOS in different continents based on Rotterdam, AES and NIH diagnostic criteria. Methods: We conducted a systematic review and meta-analysis to evaluate the prevalence of polycystic ovary syndrome in women according to (Preferred Reporting Items for Systematic Review and Meta-Analysis) PRISMA guidelines. PubMed, Scopus, Science Direct, Web of Science and Google Scholar databases were comprehensively searched until February 2021 for relevant articles. Heterogeneity between the studies was assessed using the I2 index. Begg and Mazumdar's test was used to evaluate publication bias. Results: A total of 35 studies with 12,365,646 subjects were retrieved. The mean age ranged from 10–45 years. Global prevalence of PCOS was 9.2% (95% CI: 6.8–12.5%) based on meta-analysis, our results showed that the global prevalence of PCOS was 5.5% (95% CI: 3.9–7.7%) based on NIH criteria, 11.5 (95% CI: 6.6–19.4) based on Rotterdam criteria, and 7.1% (95% CI: 2.3–20.2%) based on AES criteria. According to self-report subgroup analysis, the prevalence of PCOS was found to be 11% (95% CI: 5.2–21.8%). Conclusion: Based on the results of the present study, the prevalence of PCOS in the world was 9.2% (95% CI: 6.8–12.5%). According to the results of the present study and the high prevalence of PCOS, especially in the Africa continent, it is necessary for health systems to implement measures to timely prevent and treat this syndrome. [ABSTRACT FROM AUTHOR]

Background: Homologous recombination deficiency (HRD) is a biomarker that predicts response to ovarian cancer treatment with poly (ADP‐ribose) polymerase (PARP) inhibitors or breast cancer treatment with first‐line platinum‐based chemotherapy. However, there are few studies on the prognosis of lung cancer patients treated with immune checkpoint inhibitor (ICI) therapy using HRD as a biomarker. Methods: We studied the relationship between HRD status and the effectiveness of first‐line ICI‐based therapy in EGFR/ALK wild‐type metastatic non‐small cell lung cancer patients (NSCLC) patients. Results: This study included 22 treatment naïve NSCLC patients. The HRD score ranged from −26.37 to 92.34, with an average of 24.57. Based on analysis of the progression‐free survival (PFS) data from the included NSCLC patients, threshold traversal was carried out. HRD (+) was defined as an HRD score of 31 or higher. Kaplan–Meier PFS survival analysis showed prolonged median PFS (mPFS) in NSCLC patients with HRD (+) versus HRD (−) (N/A vs. 7.0 ms, log‐rank p = 0.029; HR 0.20, 95% CI: 0.04–0.96, likelihood‐ratio p = 0.03). In patients with PD‐L1 TPS ≥50% and HRD score ≥31 (co‐status high), the mPFS was temporarily not reached during the follow‐up period. In patients with PD‐L1 TPS <1% and HRD score <31, the mPFS was 3 ms. Cox regression analysis showed that the hazard ratio of the co‐status was 0.14 (95% CI: 0.04–0.54), which was a good prognostic factor, and the prognostic effect of co‐status was better than that of HRD score alone. Conclusion: The HRD status can be identified as an independent significance in NSCLC patients treated with first‐line ICI‐based therapy. [ABSTRACT FROM AUTHOR]

Background: The influence of alcohol intake on metabolic dysfunction‐associated fatty liver disease (MAFLD) development and remission remains unclear; thus, we aimed to investigate their longitudinal associations. Methods: This observational cohort study included 6349 patients who underwent more than two health check‐ups over >2 years between April 2013 and March 2021. Generalized estimation equations were used to analyse the longitudinal associations between changes in alcohol intake and MAFLD according to repeated measures at baseline and the most recent stage. Results: The MAFLD development and remission rates were 20.4 and 5.1 and 9.1 and 4.7% in men and women, respectively. Although alcohol consumption was not a significant factor for MAFLD development, consuming 0.1–69.9 g/week (odds ratio [OR]: 0.672, 95% confidence interval [CI]: 0.469–0.964, p <.05) and ≥280 g/week were significant factors for MAFLD development in males (OR: 1.796, 95% CI: 1.009–3.196, p <.05) and females (OR: 16.74, 95% CI: 3.877–72.24, p <.001). Regardless of quantity and frequency, alcohol consumption was not a significant factor for MAFLD remission. Several noninvasive liver fibrosis scores were significantly associated with alcohol intake quantity and frequency in males with MAFLD development and remission (p <.05). The nonalcoholic fatty liver disease fibrosis score differed significantly between males with and without reduced alcohol intake (p <.05) who showed MAFLD remission. Conclusions: Although the influence of alcohol intake on MAFLD development and remission differed, alcohol consumption was not beneficial for MAFLD remission in either sex. Alcohol intake reduction or cessation is recommended to prevent liver fibrosis, even in those who achieve MAFLD remission. [ABSTRACT FROM AUTHOR]

Summary: Human skeletal muscle mitochondria regulate energy expenditure. Research has shown that the functionality of muscle mitochondria is altered in subjects with overweight, as well as in response to nutrient excess and calorie restriction. Two metabolic features of obesity and overweight are (1) incomplete muscular fatty acid oxidation and (2) increased circulating lactate levels. In this study, I propose that these metabolic disturbances may originate from a common source within the muscle mitochondrial electron transport system. Specifically, a reorganization of the supramolecular structure of the electron transport chain could facilitate the maintenance of readily accessible coenzyme Q pools, which are essential for metabolizing lipid substrates. This approach is expected to maintain effective electron transfer, provided that there is sufficient complex III to support the Q‐cycle. Such an adaptation could enhance fatty acid oxidation and prevent mitochondrial overload, thereby reducing lactate production. These insights advance our understanding of the molecular mechanisms underpinning metabolic dysregulation in overweight states. This provides a basis for targeted interventions in the quest for metabolic health. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is associated with obesity and, therefore, it is important to target both overweight and hyperglycaemia. Glucagon plays important roles in glucose, amino acid and fat metabolism and may also regulate appetite and energy expenditure. These physiological properties are currently being exploited therapeutically in several compounds, most often in combination with glucagon‐like peptide‐1 (GLP‐1) agonism in the form of dual agonists. With this combination, increases in hepatic glucose production and hyperglycaemia, which would be counterproductive, are largely avoided. In multiple randomized trials, the co‐agonists have been demonstrated to lead to significant weight loss and, in participants with T2DM, even improved glycated haemoglobin (HbA1c) levels. In addition, significant reductions in hepatic fat content have been observed. Here, we review and discuss the studies so far available. Twenty‐six randomized trials of seven different GLP‐1 receptor (GLP‐1R)/glucagon receptor (GCGR) co‐agonists were identified and reviewed. GLP‐1R/GCGR co‐agonists generally provided significant weight loss, reductions in hepatic fat content, improved lipid profiles, insulin secretion and sensitivity, and in some cases, improved HbA1c levels. A higher incidence of adverse effects was present with GLP‐1R/GCGR co‐agonist treatment than with GLP‐1 agonist monotherapy or placebo. Possible additional risks associated with glucagon agonism are also discussed. A delicate balance between GLP‐1 and glucagon agonism seems to be of particular importance. Further studies exploring the optimal ratio of GLP‐1 and glucagon receptor activation and dosage and titration regimens are needed to ensure a sufficient safety profile while providing clinical benefits. [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations of metabolic score for insulin resistance (METS‐IR) with all‐cause and cardiovascular disease (CVD)‐specific mortality and the potential mediating role of biological ageing. Methods: A cohort of 19 204 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 was recruited for this study. Cox regression models, restricted cubic splines, and Kaplan–Meier survival curves were used to determine the relationships of METS‐IR with all‐cause and CVD‐specific mortality. Mediation analyses were performed to explore the possible intermediary role of biological ageing markers, including phenotypic age (PhenoAge) and biological age (BioAge). Results: During a median follow‐up of 9.17 years, we observed 2818 deaths, of which 875 were CVD‐specific. Multivariable Cox regression showed that the highest METS‐IR level (Q4) was associated with increased all‐cause (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.14–1.67) and CVD mortality (HR 1.52, 95% CI 1.10–2.12) compared with the Q1 level. Restricted cubic splines showed a nonlinear relationship between METS‐IR and all‐cause mortality. Only METS‐IR above the threshold (41.02 μg/L) was positively correlated with all‐cause death. METS‐IR had a linear positive relationship with CVD mortality. In mediation analyses, we found that PhenoAge mediated 51.32% (p < 0.001) and 41.77% (p < 0.001) of the association between METS‐IR and all‐cause and CVD‐specific mortality, respectively. For BioAge, the mediating proportions of PhenoAge were 21.33% (p < 0.001) and 15.88% (p < 0.001), respectively. Conclusions: This study highlights the detrimental effects of insulin resistance, as measured by METS‐IR, on all‐cause and CVD mortality. Moreover, it underscores the role of biological ageing in mediating these associations, emphasizing the need for interventions targeting both insulin resistance and ageing processes to mitigate mortality risks in metabolic disorders. [ABSTRACT FROM AUTHOR]

Obesity has become a major global problem that significantly confers an increased risk of developing life‐threatening complications, including type 2 diabetes mellitus, fatty liver disease and cardiovascular diseases. Protein arginine methyltransferases (PRMTs) are enzymes that catalyse the methylation of target proteins. They are ubiquitous in eukaryotes and regulate transcription, splicing, cell metabolism and RNA biology. As a key, epigenetically modified enzyme, protein arginine methyltransferase 1 (PRMT1) is involved in obesity‐related metabolic processes, such as lipid metabolism, the insulin signalling pathway, energy balance and inflammation, and plays an important role in the pathology of obesity‐related metabolic disorders. This review summarizes recent research on the role of PRMT1 in obesity‐related metabolic disorders. The primary objective was to comprehensively elucidate the functional role and regulatory mechanisms of PRMT1. Moreover, this study attempts to review the pathogenesis of PRMT1‐mediated obesity‐related metabolic disorders, thereby offering pivotal information for further studies and clinical treatment. [ABSTRACT FROM AUTHOR]

Obesity has a pivotal and multifaceted role in pain associated with osteoarthritis (OA), extending beyond the mechanistic influence of BMI. It exerts its effects both directly and indirectly through various modifiable risk factors associated with OA-related pain. Adipose tissue dysfunction is highly involved in OA-related pain through local and systemic inflammation, immune dysfunction, and the production of pro-inflammatory cytokines and adipokines. Adipose tissue dysfunction is intricately connected with metabolic syndrome, which independently exerts specific effects on OA-related pain, distinct from its association with BMI. The interplay among obesity, adipose tissue dysfunction and metabolic syndrome influences OA-related pain through diverse pain mechanisms, including nociceptive pain, peripheral sensitization and central sensitization. These complex interactions contribute to the heightened pain experience observed in individuals with OA and obesity. In addition, pain management strategies are less efficient in individuals with obesity. Importantly, therapeutic interventions targeting obesity and metabolic syndrome hold promise in managing OA-related pain. A deeper understanding of the intricate relationship between obesity, metabolic syndrome and OA-related pain is crucial and could have important implications for improving pain management and developing innovative therapeutic options in OA. In this Review, the authors explore the complex interactions between osteoarthritis-related pain and obesity, adipose tissue dysfunction and metabolic syndrome, and discuss how knowledge of these relationships could help improve pain management and identify new therapeutic options. Key points: Obesity serves as an important risk factor for pain in osteoarthritis (OA) and is associated with all modifiable risk factors related to OA-related pain. Adipose tissue dysfunction has a specific role in OA-related pain independently of BMI. Serum and synovial fluid levels of leptin are closely associated with OA-related pain after adjustment for BMI, whereas the role of adiponectin in OA pain is controversial. Metabolic syndrome is associated with OA-related pain independently of BMI. Obesity modulates nociceptive, neuropathic-like and nociplastic pain through neuromodulators and both peripheral and central sensitization. Therapeutics used in the treatment of obesity and metabolic syndrome could also hold promise for the management of OA-related pain, particularly GLP1R agonists. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic intracranial hypertension (IIH) is a neurometabolic disease with an increasing incidence. The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity. Methods: This is a prospective case–control study with collection of cerebrospinal fluid (CSF), serum, and clinical data from new‐onset, treatment‐naïve patients with IIH (n = 60). Patients were included consecutively from 2 tertiary headache centers in Denmark, and age, sex, and body mass index (BMI) ‐matched healthy controls (n = 35) were recruited. Clinical data were retrieved at ocular remission (n = 55). Samples were analyzed using non‐targeted mass spectrometry. Results: Serum sphingosine 1‐phosphate (S1P), adenosine, and glutamate were 0.46‐fold (q < 0.0001), 0.25‐fold (q = 0.0048), and 0.44‐fold (q < 0.0001) lower, respectively, in IIH. CSF stearoyl‐lysophosphatidylcholine (LysoPC‐18) and 2‐palmitoyl‐lysophosphatidylcholine (LysoPC‐16) were 0.42 (q = 0.0025) and 0.37 (q < 0.001) ‐fold lower. LysoPC‐18 was higher in patients with moderate–severe versus mild papilledema (p = 0.022). LysoPC‐18 correlated positively with retinal nerve fiber layer thickness (p = 0.0012, r = 0.42) and inversely with mean deviation on automated perimetry (p = 0.01, r = −0.35). Higher baseline serum S1P (p = 0.018) and lower CSF LysoPC‐16 (p = 0.003) were associated with optic nerve atrophy at ocular remission. Pathway analysis suggests dysregulated lipid metabolism and redox disturbances in new‐onset IIH. Interpretation: We identify perturbed metabolism in new‐onset IIH. S1P and LysoPC‐16 demonstrate potential prognostic value due to association with subsequent optic nerve atrophy. This association between specific, differential metabolites and outcome provides substantial evidence for novel biomarkers of clinical significance that should be the focus of further targeted studies. ANN NEUROL 2024;96:595–607 [ABSTRACT FROM AUTHOR]

Background: Glucosamine is a dietary supplement commonly used to support joint health. However, there has been interest in exploring other effects of glucosamine on health outcomes due to its ant‐inflammation effect. Objective: This study compared the risks of major adverse liver outcomes (MALOs) between regular users and non‐users of glucosamine among patients with type 2 diabetes and metabolic dysfunction associated steatotic liver disease (MASLD) using the data from a large prospective cohort study. Methods: Demographic, anthropometric, laboratory and medication prescription information among 18 753 patients with type 2 diabetes and MASLD was obtained from the UK Biobank. MASLD was identified based on hepatic steatosis defined by fatty liver index ≥60 plus the presence of any clues of metabolic dysregulation and cardio‐metabolic risk factors, excluding patients with moderate to severe alcohol consumption. Results: During a mean follow‐up of 11.4 years, 826 incident MALOs events were recorded. Patients not regularly using glucosamine compared with patients using glucosamine showed a significantly higher risk of the composite MALOs (HR 1.36, 95% confidence interval [CI] 1.09–1.69) as well as most individual MALOs except for ascites. The multivariable‐adjusted HRs of MALOs within 3, 5 and 10 years among non‐users of glucosamine compared with regular users were 1.79 (95% CI.69–2.03), 1.88 (95% CI 1.21–2.54) and 1.32 (95% CI 1.05–1.72), respectively. Further subgroup analyses in participants with different baseline characteristics and sensitivity analyses excluding participants who regularly took any other supplements and participants who used self‐reports to diagnose diabetes confirmed the findings. Conclusions: The present study indicated that habitual use of glucosamine was associated with a low risk of individual and composite MALOs among patients with type 2 diabetes and MASLD. [ABSTRACT FROM AUTHOR]

Seaweed polysaccharides (SPs) obtained from seaweeds are a class of functional prebiotics. SPs can regulate glucose and lipid anomalies, affect appetite, reduce inflammation and oxidative stress, and therefore have great potential for managing metabolic syndrome (MetS). SPs are poorly digested by the human gastrointestinal tract but are available to the gut microbiota to produce metabolites and exert a series of positive effects, which may be the mechanism by which SPs render their anti-MetS effects. This article reviews the potential of SPs as prebiotics in the management of MetS-related metabolic disturbances. The structure of SPs and studies related to the process of their degradation by gut bacteria and their therapeutic effects on MetS are highlighted. In summary, this review provides new perspectives on SPs as prebiotics to prevent and treat MetS. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound. Its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after exposure to BPA (10 mg/L via drinking water for 90 days). Four groups were taken in this study – Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress, and antioxidants were also determined. HFD + BPA group rats showed a significant decline in memory function in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule-associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor– kappa B (NF-КB) in the brain. Obesity also caused significant (p < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (p < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases. [ABSTRACT FROM AUTHOR]

There may be an increased risk of metabolic disorders, such as rumen acidosis, in cattle fed high‐concentrate diets, particularly those from Bos taurus indicus genotypes, which have shown to be more sensitive to ruminal acidification. Therefore, this study aimed to estimate (co)variance components and identify genomic regions and pathways associated with ruminal acidosis in feedlot Nellore cattle fed high‐concentrate diets. It was utilized a dataset containing a total of 642 Nellore bulls that were genotyped from seven feedlot nutrition studies. The GGP Indicus 35k panel was used with the single step genome‐wide association study methodology in which the effects of the markers were obtained from the genomic values estimated by the GBLUP model. A bivariate model to estimate genetic correlations between the economically important traits and indicator traits for acidosis was used. The traits evaluated in this study that were nutritionally related to rumen acidosis included average daily gain (ADG), final body weight, time spent eating (TSE), time spent ruminating, rumenitis score (RUM), rumen absorptive surface area (ASA), rumen keratinized layer thickness (KER) and hot carcass weight (HCW). The identified candidate genes were mainly involved in the negative or non‐regulation of the apoptotic process, salivary secretion, and transmembrane transport. The genetic correlation between HCW and ASA was low positive (0.27 ± 0.23), and between ADG and ASA was high moderate (0.58 ± 0.59). A positive genetic correlation between RUM and all performance traits was observed, and TSE correlated negatively with HCW (−0.33 ± 0.21), ASA (−0.75 ± 0.48), and KER (−0.40 ± 0.27). The genetic association between economically important traits and indicator traits for acidosis suggested that Nellore cattle may be more sensitive to acidosis in feedlot systems. [ABSTRACT FROM AUTHOR]

Flavin containing monooxygenase 3 (FMO3) is a member of the flavin monooxygenase family, which can oxidize the precursor Trimethylamine (TMA) provided from food to produce Trimethylamine N-oxide (TMAO). The autosomal recessive inherited disease caused by partial functional loss of Fmo3 gene, which leads to excessive excretion of TMA in body fluids and emits fishy odor, is called Fish Odor Syndrome or Trimethylaminuria. This disease has been documented for 3,000 years ago and was first reported in the case report in 1970. FMO3 mainly exists in the liver and can participate in the TMA-TMAO metabolic balance in intestinal microorganisms, liver, and kidneys, closely related to insulin resistance, diabetes, cholesterol metabolism, and cardiovascular disease. Due to its wide range of catalytic substrates and low susceptibility to metabolite accumulation, its role in drug metabolism, new drug development, and discovery of new drug targets are increasingly valued. This review will summarize the research progress on the metabolic process and localization of FMO3, congenital genetic defects, metabolic diseases, and its related possible mechanisms. [ABSTRACT FROM AUTHOR]

Background: Male androgenetic alopecia (MAA) is a multifactorial disease, with patients presenting at a younger age, which is a risk factor for many metabolic diseases. Aims: To explore the risk factors associated with early‐onset of MAA and its metabolic characteristics. Methods: Forty patients with MAA and 45 healthy controls were collected. The serum levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), total testosterone (TT), uric acid (UA), and 25‐hydroxyvitamin D (25(OH)D) were measured. Meanwhile, lipid metabolites were detected by ultra‐high‐performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Results: 37.50% MAA patients had metabolic syndrome, compared to 17.78% in control group (p < 0.05). The levels of HDL‐C, UA, and 25(OH)D were decreased in patients with MAA compared to healthy controls (p < 0.05). However, there was no significant difference in the level of TT between the two groups. Additionally, there were no significant differences in the levels of HDL‐C, UA, 25(OH)D, and TT among different grades of hair loss (p > 0.05). The lipid profile of early‐onset MAA differed significantly from healthy controls. In early‐onset MAA, the levels of ceramide (Cer) and sphingomyelin (SM) were significantly lower. Cer(d38:5) and TG(15:0/18:1/18:1) may be the biomarkers. Conclusion: Low HDL‐C, UA, and 25(OH)D may be the independent risk factors for early‐onset MAA. Abnormal lipid metabolism was observed in early‐onset MAA, wherein Cer and SM may serve as protective factors. [ABSTRACT FROM AUTHOR]

β‐arrestin2, a member of the arrestin family, mediates the desensitization and internalization of most G protein‐coupled receptors (GPCRs) and functions as a scaffold protein in signalling pathways. Previous studies have demonstrated that β‐arrestin2 expression is dysregulated in malignant tumours, fibrotic diseases, cardiovascular diseases and metabolic diseases, suggesting its pathological roles. Transcription and post‐transcriptional modifications can affect the expression of β‐arrestin2. Furthermore, post‐translational modifications, such as phosphorylation, ubiquitination, SUMOylation and S‐nitrosylation affect the cellular localization of β‐arrestin2 and its interaction with downstream signalling molecules, which further regulate the activity of β‐arrestin2. This review summarizes the structure and function of β‐arrestin2 and reveals the mechanisms involved in the regulation of β‐arrestin2 at multiple levels. Additionally, recent studies on the role of β‐arrestin2 in some major diseases and its therapeutic prospects have been discussed to provide a reference for the development of drugs targeting β‐arrestin2. [ABSTRACT FROM AUTHOR]

Obesity compromises metabolic flexibility and increases specific immune responses. Fasting forces metabolic flexibility and alters glucose, fatty acids, glycerol, and amino acids to maintain blood glucose and energy balance. Intermittent fasting (IF) lowers inflammation and opposes metabolic dysfunction during obesity. IF can improve glucose metabolism independent of changes in obesity. Gut microbiota composition altered by IF triggers changes in immunity and metabolism. Intermittent fasting (IF) modifies cell- and tissue-specific immunometabolic responses that dictate metabolic flexibility and inflammation during obesity and type 2 diabetes (T2D). Fasting forces periods of metabolic flexibility and necessitates increased use of different substrates. IF can lower metabolic inflammation and improve glucose metabolism without lowering obesity and can influence time-dependent, compartmentalized changes in immunity. Liver, adipose tissue, skeletal muscle, and immune cells communicate to relay metabolic and immune signals during fasting. Here we review the connections between metabolic and immune cells to explain the divergent effects of IF compared with classic caloric restriction (CR) strategies. We also explore how the immunometabolism of metabolic diseases dictates certain IF outcomes, where the gut microbiota triggers changes in immunity and metabolism during fasting. [ABSTRACT FROM AUTHOR]

Kidney replacement therapy (KRT) can provide lifesaving support for children with severely impaired kidney function. The decision about who needs KRT and when is often complex. Many acute kidney problems will resolve with conservative maanagemenent but some children with chronic or acute kidney impairment will find themselves in a position where KRT is required either as a bridge to recovery or kidney transplantation. Less commonly, children with metabolic disorders may find that the ability of their own kidneys is overwhelmed by excessive production of certain metabolites. These children may also benefit from short term KRT. This article aims to help paediatricians in training understand which children need kidney replacement therapy, the various types of treatment available, and when they are used. [ABSTRACT FROM AUTHOR]

Given its nonnegligible role in metabolic homeostasis, adipose tissue has been the target for treating metabolic disorders such as obesity, diabetes and cardiovascular diseases. Besides its lipolytic function, adipose thermogenesis has gained increased interest due to the irreplaceable contribution to dissipating energy to restore equilibrium, and its therapeutic effects have been testified in various animal models. In this review, we will brief about the canonical cold-stimulated adipose thermogenic mechanisms, elucidate on the exercise- and intermittent fasting-induced adipose thermogenic mechanisms, with a focus on the similarities and disparities among these signaling pathways, in an effort to uncover the overlapped and specific targets that may yield potent therapeutic efficacy synergistically in improving metabolic health. • Adipose thermogenic mechanisms induced by cold exposure, exercise and intermittent fasting share similar signaling pathways. • Certain adipose thermogenic mechanisms induced by exercise are distinctive. • Adipose thermogenesis has been applied in treatment for various diseases. • Similarities and disparities in adipose thermogenic mechanisms shed new light on treating diseases. [ABSTRACT FROM AUTHOR]

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The objective of this study was to analyse an individual whose remains are characterised by early deciduous tooth loss and multi-focal lesions on the post-cranial skeleton. Skeletal remains of an immature individual buried between 1770 and 1849 in London. The remains were examined by visual macroscopic inspection, supplemented by radiographic examination of the mandible and maxillae. A differential diagnosis with possible conditions, frequent in this archaeological context, was conducted. A comprehensive examination of dental lesions was performed to investigate the aetiologies of deciduous tooth loss. The individual exhibited a mosaic of skeletal and dental pathological changes, including premature loss of deciduous dentition, premature eruption of permanent teeth generalised bone loss in both the mandible and maxilla; osteomyelitis of the left radius; osteolytic lesion on the body of the second lumbar vertebra, and marked expansions of the rib shafts due to sub-periosteal new bone formation. A differential diagnosis considered indicates that the pathological changes of the individual were most likely associated with a comorbidity involving hypophosphatasia and tuberculosis. We present in this study several oral signs that could alert paleopathologists and bioarcheologists to systematically consider the potential of a condition that is rarely encountered in archaeological contexts. Due to poor preservation, this study was confined to the analysis of a partial maxilla and mandible, a left radius shaft and the axial skeleton (rib heads and vertebrae) of the individual. Further radiographic, histological and genetic analyses would confirm the diagnosis. [ABSTRACT FROM AUTHOR]

Context Surrogate measures of childhood and adolescent obesity have impaired the understanding of the relationship of body composition with insulin resistance in the young population. Objective We aim to examine the longitudinal associations of directly measured total fat mass, trunk fat mass, and lean mass with the risk of hyperglycemia, hyperinsulinemia, and insulin resistance from ages 15 to 24 years, the mediation path through which lipids and inflammation influence insulin resistance, and whether increased fat mass temporally precede insulin resistance. Methods We studied 3160 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, who had complete dual-energy x-ray absorptiometry measure and fasting blood samples at age 15 years and repeated measures at ages 17- and 24-years clinic visit. Fasting glucose greater than 6.1 mmol/L, insulin greater than 11.78 mU/L, and homeostatic model assessment for insulin resistance (HOMA-IR) greater than or equal to the 75th percentile were categorized as hyperglycemia, hyperinsulinemia, and high insulin resistance, respectively. Longitudinal associations were examined with generalized logit-mixed-effect models, while mediation and temporal path analyses were examined using structural equation models, adjusting for cardiometabolic and lifestyle factors. Results Among 3160 participants (51% female), fat mass and lean mass increased linearly both in males and females, while glucose, insulin, and HOMA-IR had a U-shaped course from age 15 through 24 years. After full adjustment, each 1-kg cumulative increase in total fat mass (odds ratio 1.12 [95% CI, 1.11-1.13]) and trunk fat mass (1.21 [1.19-1.23]) from ages 15 through 24 years were associated with a progressively worsening risk of high insulin resistance as well as hyperglycemia and hyperinsulinemia. The association of increased total fat mass with increased insulin resistance was partly mediated by triglycerides (9% mediation). In the temporal path analysis, higher total fat mass at age 15 years was associated with higher insulin resistance at age 17 years, but not vice versa. Higher total fat mass at age 17 years was bidirectionally associated with higher insulin resistance at 24 years. Conclusion Mid-adolescence may be an optimal time for interrupting the worsening fat mass–insulin resistance pathologic cycle and attenuating the risk of progressively worsening metabolic dysfunction before young adulthood. [ABSTRACT FROM AUTHOR]

Purpose: Sleeve gastrectomy (SG) is the most performed metabolic and bariatric surgery (MBS). However, with the increase of SG in different regions, recurrent weight gain after SG is challenging for bariatric surgeons. We introduce a modified operation with a long, narrow pouch in RYGB (LN-RYGB) for weight regain after SG which enhanced the restrictive function in RYGB. Methods and Results: The LN-RYGB has a longer and narrow gastric pouch for 10 cm. The length of small Roux and biliopancreatic are the same as RYGB. As a revisional surgery, the post-1 year excess weight loss percentage (%EWL) was 63.1% and total weight loss percentage (%TWL) was 29.1% in 5 cases. Conclusion: LN-RYGB is an optional treatment for recurrent weight gain after SG; a randomized control trial is needed to verify the long-term effect of LN-RYGB. [ABSTRACT FROM AUTHOR]