Search

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has introduced the medical community to the phenomenon of long COVID, a condition characterized by persistent symptoms following the resolution of the acute phase of infection. Among the myriad of symptoms reported by long COVID sufferers, chronic fatigue, cognitive disturbances, and exercise intolerance are predominant, suggesting systemic alterations beyond the initial viral pathology. Emerging evidence has pointed to mitochondrial dysfunction as a potential underpinning mechanism contributing to the persistence and diversity of long COVID symptoms. This review aims to synthesize current findings related to mitochondrial dysfunction in long COVID, exploring its implications for cellular energy deficits, oxidative stress, immune dysregulation, metabolic disturbances, and endothelial dysfunction. Through a comprehensive analysis of the literature, we highlight the significance of mitochondrial health in the pathophysiology of long COVID, drawing parallels with similar clinical syndromes linked to post-infectious states in other diseases where mitochondrial impairment has been implicated. We discuss potential therapeutic strategies targeting mitochondrial function, including pharmacological interventions, lifestyle modifications, exercise, and dietary approaches, and emphasize the need for further research and collaborative efforts to advance our understanding and management of long COVID. This review underscores the critical role of mitochondrial dysfunction in long COVID and calls for a multidisciplinary approach to address the gaps in our knowledge and treatment options for those affected by this condition. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a multisystemic disorder of pregnancy that not only causes perinatal mortality and morbidity but also has a long-term toll on the maternal and fetal cardiovascular system. Women diagnosed with PE are at greater risk for the subsequent development of hypertension, ischemic heart disease, cardiomyopathy, cerebral edema, seizures, and end-stage renal disease. Although PE is considered heterogeneous, inefficient extravillous trophoblast (EVT) migration leading to deficient spiral artery remodeling and increased uteroplacental vascular resistance is the likely initiation of the disease. The principal pathophysiology is placental hypoxia, causing subsequent oxidative stress, leading to mitochondrial dysfunction, mitophagy, and immunological imbalance. The damage imposed on the placenta in turn results in the "stress response" categorized by the dysfunctional release of vasoactive components including oxidative stressors, proinflammatory factors, and cytokines into the maternal circulation. These bioactive factors have deleterious effects on systemic endothelial cells and coagulation leading to generalized vascular dysfunction and hypercoagulability. A better understanding of these metabolic factors may lead to novel therapeutic approaches to prevent and treat this multisystemic disorder. In this review, we connect the hypoxic-oxidative stress and inflammation involved in the pathophysiology of PE to the resulting persistent cardiovascular complications in patients with preeclampsia. [ABSTRACT FROM AUTHOR]

Yueyuan Wang,* Bo Lv,* Kai Fan, Cunjin Su, Delai Xu, Jie Pan Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Pan; Delai Xu, Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, People’s Republic of China, Email panzy1122@163.com; xdlsuzhou@163.comPurpose: Parkinson’s disease (PD) is a common neurodegenerative disease that severely affects patients’ daily lives and places a significant burden on the global economy. There are currently no specific biomarkers for distinguishing between the different stages of PD.Methods: We divided 78 mice into six equal groups, including five model PD groups (W1–W5; based on the PD stage induced by length of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/propofol induction time) and a control group. Then, we used metabolomics technology to detect the serum small-molecule metabolites present in each group. Ultimately, we screened for potential biomarkers using the variable importance in the projection of the orthogonal partial least squares discriminant analysis and the coefficient value of LASSO ordinal logistic regression.Results: We identified 12 potential biomarkers, including dehydroepiandrosterone sulfate, pipecolic acid, N-acetylleucine, 2-aminoadipic acid, L-tyrosine, uric acid, and 5-hydroxyindoleacetaldehyde. Pathway analysis revealed their involvement in amino acid metabolism, caffeine metabolism, steroid hormone biosynthesis, and purine metabolism. Additionally, the receiver operating characteristic curve indicated that a biomarker panel comprising the 12 biomarkers could differentiate between the different PD stages.Conclusion: Different PD stages are characterized by different metabolites. The biomarkers identified in this study are helpful to understand the PD process.Keywords: Parkinson’s disease, metabolomics, biomarkers, metabolic disturbances, LC–MS

Objective: Obesity represents a significant global health challenge characterized by chronic low-grade inflammation and metabolic dysregulation. The hypothalamus, a key regulator of energy homeostasis, is particularly susceptible to obesity's deleterious effects. This study investigated the role of the immunoproteasome, a specialized proteasomal complex implicated in inflammation and cellular homeostasis, during metabolic diseases. Methods: The levels of the immunoproteasome β5i subunit were analyzed by immunostaining, western blotting, and proteasome activity assay in mice fed with either a high-fat diet (HFD) or a regular diet (CHOW). We also characterized the impact of autophagy inhibition on the levels of the immunoproteasome β5i subunit and the activation of the AKT pathway. Finally, through confocal microscopy, we analyzed the contribution of β5i subunit inhibition on mitochondrial function by flow cytometry and mitophagy assay. Results: Using an HFD-fed obese mouse model, we found increased immunoproteasome levels in hypothalamic POMC neurons. Furthermore, we observed that palmitic acid (PA), a major component of saturated fats found in HFD, increased the levels of the β5i subunit of the immunoproteasome in hypothalamic neuronal cells. Notably, the increase in immunoproteasome expression was associated with decreased autophagy, a critical cellular process in maintaining homeostasis and suppressing inflammation. Functionally, PA disrupted the insulin-glucose axis, leading to reduced AKT phosphorylation and increased intracellular glucose levels in response to insulin due to the upregulation of the immunoproteasome. Mechanistically, we identified that the protein PTEN, a key regulator of insulin signaling, was reduced in an immunoproteasome-dependent manner. To further investigate the potential therapeutic implications of these findings, we used ONX-0914, a specific immunoproteasome inhibitor. We demonstrated that this inhibitor prevents PA-induced insulin-glucose axis imbalance. Given the interplay between mitochondrial dysfunction and metabolic disturbances, we explored the impact of ONX-0914 on mitochondrial function. Notably, ONX-0914 preserved mitochondrial membrane potential and attenuated mitochondrial ROS production in the presence of PA. Moreover, we found that ONX-0914 reduced mitophagy in the presence of PA. Conclusions: Our findings strongly support the pathogenic involvement of the immunoproteasome in hypothalamic neurons in the context of HFD-induced obesity and metabolic disturbances. Targeting the immunoproteasome highlights a promising therapeutic strategy to mitigate the detrimental effects of obesity on the insulin-glucose axis and cellular homeostasis. This study provides valuable insights into the mechanisms driving obesity-related metabolic diseases and offers potential avenues for developing novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

High-voltage electrical injuries, especially from lightning strikes, can cause life-threatening complications due to extreme temperature and voltage exposure. While burns and cardiac complications have been widely described, the documentation of metabolic imbalances, particularly hypokalemia, has not been as prevalent. This report focuses on a patient with profound transient hypokalemia following a lightning strike, alongside a review of three similar cases of transient hypokalemia from the literature. Our patient, a previously healthy young man, was struck by lightning and subsequently suffered transient hypokalemia with lower extremity sensory changes, which resolved after the normalization of serum potassium levels. While the exact underlying mechanisms of transient hypokalemia following high-voltage electrical injuries are unknown, we propose a multifactorial mechanism, which includes massive intracellular shifts of potassium due to elevated epinephrine levels and the prevention of potassium efflux through the electrical disruption of voltage-gated potassium channels. Our report underscores the importance of recognizing hypokalemia in patients with high-voltage electrical injuries and contributes to the understanding of the complex mechanisms involved. Further research is necessary to understand the connection between cellular changes induced by high-voltage exposure and their effects on metabolism, particularly in relation to hypokalemia. [ABSTRACT FROM AUTHOR]

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole‐induced PCOS‐related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p <.01) and relative ovary weight (p <.05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p <.01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p <.01, p <.05), and follicle‐stimulating hormone (FSH) levels were increased (p <.05). SA administration also decreased triglyceride (TG) (p <.01) and total cholesterol (TC) levels (p <.05) and increased high‐density lipoprotein cholesterol (HDL‐C) levels (p <.01), thereby alleviating letrozole‐induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), reduced the activation of transforming growth factor‐β1 (TGF‐β1)/Smads, and decreased collagen I, α‐smooth muscle actin (α‐SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole‐induced PCOS. [ABSTRACT FROM AUTHOR]

There is a growing body of research showing the potential health benefits of resveratrol, including anti-inflammatory and antioxidant properties. This study investigates the potential effects of resveratrol on lipid profile and its impact on wound healing in a Male Albino Wistar Rats model of type 2 diabetes. 24 Male Albino Wistar Rats were rendered diabetic using a high-fat diet and an Alloxan injection. The rats were grouped into 4: Nondiabetic Control Group A (negative control), Diabetic Control Group B (positive control), Diabetic Treatment Group C (10 mg/kg resveratrol), and Diabetic Treatment Group D (20 mg/kg resveratrol). Excisional wounds were created on the dorsum of the rats and monitored for wound closure over a defined treatment period of 14 days. Body weight and fasting blood glucose levels were measured after the procedure and after the treatment respectively. Blood samples were collected on the 15th day by cardiac puncture to assess lipid profile parameters. Resveratrol administration positively modified body weight, blood glucose, and lipid profile, reducing total cholesterol, triglycerides, low-density lipoprotein, and elevation of high-density lipoprotein levels. Resveratrol supplementation not only enhanced wound healing but also alleviated dyslipidaemia in type 2 diabetic albino male rats, a common complicating factor in the management of diabetic wounds. These results imply that resveratrol might have a broad range of therapeutic applications in treating lipid profile abnormalities linked to type 2 diabetes as well as wound healing complications. [ABSTRACT FROM AUTHOR]

Aim: Drug‐related problems (DRPs) are a common cause of hospitalization in older patients. So far, these issues have been studied in hospitalized settings, and evidence on patterns and outcomes of DRPs, such as adverse drug reactions, is relatively scarce in older outpatients. The main aim of this study was to provide a comprehensive description and possible solutions for DRPs in older adults in outpatient settings. Methods: The study was carried out from January 2015 to September 2021 in a tertiary hospital in north India. Patients aged ≥50 years with DRPs were enrolled. DRPs causing hospitalization, drug interactions and drug–disease interactions were identified, along with preventive measures. Results: Of 10 400 patients registered, 1031 DRPs occurred in 666 patients (9.9%). Adverse drug reactions were the major DRPs (n = 933, 8.9%). Metabolic disorders were the commonest DRP in individuals aged ≥65 years compared with gastrointestinal disorders in the 50–64 years group. Drug interactions and drug–disease interactions contributed to 20.1% and 7.9% of patients, respectively. Nearly 15.8% of DRPs directly led to hospitalization, with drug‐induced metabolic disturbances and movement disorders as the common causes. The Naranjo scale was not applicable in 35.3% of patients, and drug interactions were the commonest cause. Frequent monitoring, omission of unnecessary drugs, slow titration and proper instructions on therapy, together, could avoid one‐third of DRPs. Conclusion: One out of 10 prescriptions of older outpatients carries a DRP. New‐onset metabolic and neurological disturbances should prompt a thorough drug history. A multifaceted holistic approach can prevent significant drug‐related morbidity and requires future evaluation. Geriatr Gerontol Int 2024; 24: 285–291. [ABSTRACT FROM AUTHOR]

Study aim: To evaluate circulating lipoproteins, glucose, insulin and the index of insulin resistance (HOMA-IR) in male Polish students with normal BMI and waist circumference (WC) in the context of their physical activity.

Background: Psychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission. Methods: Between 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances. Results: A total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission. Conclusion: The observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IVDD) is a common degenerative condition, which is thought to be a major cause of lower back pain (LBP). However, the etiology and pathophysiology of IVDD are not yet completely clear. To examine potential causal effects of modifiable risk factors on IVDD. Bidirectional Mendelian randomization (MR) study. Genome-wide association studies (GWAS) with sample sizes between 54,358 and 766,345 participants. Outcomes included (1) modifiable risk factors associated with IVDD use in the forward MR; and (2) modifiable risk factors that were determined to have a causal association with IVDD in the reverse MR, including smoking, alcohol intake, standing height, education level, household income, sleeplessness, hypertension, hip osteoarthritis, HDL, triglycerides, apolipoprotein A-I, type 2 diabetes, fasting glucose, HbA1c, BMI and obesity trait. We obtained genetic variants associated with 33 exposure factors from genome-wide association studies. Summary statistics for IVDD were obtained from the FinnGen consortium. The risk factors of IVDD were analyzed by inverse variance weighting method, MR-Egger method, weighted median method, MR-PRESSO method and multivariate MR Method. Reverse Mendelian randomization analysis was performed on risk factors found to be caustically associated with IVDD in the forward Mendelian randomization analysis. The heterogeneity of instrumental variables was quantified using Cochran's Q statistic. Genetic predisposition to smoking (OR=1.221, 95% CI: 1.068–1.396), alcohol intake (OR=1.208, 95% CI: 1.056–1.328) and standing height (OR=1.149, 95% CI: 1.072–1.231) were associated with increased risk of IVDD. In addition, education level (OR=0.573, 95%CI: 0.502–0.654)and household income (OR=0.614, 95%CI: 0.445–0.847) had a protective effect on IVDD. Sleeplessness (OR=1.799, 95%CI: 1.162–2.783), hypertension (OR=2.113, 95%CI: 1.132–3.944) and type 2 diabetes (OR=1.069, 95%CI: 1.024–1.115) are three important risk factors causally associated with the IVDD. In addition, we demonstrated that increased levels of triglycerides (OR=1.080, 95%CI:1.013–1.151), fasting glucose (OR=1.189, 95%CI:1.007–1.405), and HbA1c (OR=1.308, 95%CI:1.017–1.683) could significantly increase the odds of IVDD. Hip osteoarthritis, HDL, apolipoprotein A-I, BMI and obesity trait factors showed bidirectional causal associations with IVDD, therefore we considered the causal associations between these risk factors and IVDD to be uncertain. This MR study provides evidence of complex causal associations between modifiable risk factors and IVDD. It is noteworthy that metabolic disturbances appear to have a more significant effect on IVDD than biomechanical alterations, as individuals with type 2 diabetes, elevated triglycerides, fasting glucose, and elevated HbA1c are at higher risk for IVDD, and the causal association of obesity-related characteristics with IVDD incidence is unclear. These findings provide new insights into potential therapeutic and prevention strategies. Further research is needed to clarify the mechanisms of these risk factors on IVDD. [ABSTRACT FROM AUTHOR]

BackgroundPsychiatric patients are at high risk of readmission, and a high body mass index has previously been shown as a risk factor. We sought to replicate this finding and 1) to prospectively assess the association of metabolic syndrome and its five components with readmission in psychiatric hospitals and 2) to identify other clinical and sociodemographic predictors of readmission.MethodsBetween 2007 and 2019, data on 16727 admissions of 7786 adult and elderly patients admitted to the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to the International Diabetes Federation definition. Cox frailty models were used to investigate the associations between readmission and metabolic disturbances.ResultsA total of 2697 (35%) patients were readmitted to our psychiatric hospital. Novel risk factors for readmission in non-smokers were identified, including being overweight (HR=1.26; 95%CI=[1.05; 1.51]) or obese (HR=1.33; 95%CI=[1.08; 1.62]), displaying hypertriglyceridemia (HR=1.21; 95%CI=[1.04; 1.40]) and metabolic syndrome (HR=1.26; 95%CI=[1.02; 1.55]). Central obesity and hyperglycemia increased the risk of readmission when considering the Health of the Nation Outcome Scales variable. In first-episode psychosis patients, obesity (HR=2.23; 95%CI=[1.14; 4.30]) and high-density lipoprotein hypocholesterolemia (HR=1.90; 95%CI=[1.14; 3.20]) doubled the risk of readmission.ConclusionThe observed interaction between smoking and metabolic variables are compatible with a ceiling effect; metabolic variables increase the risk of readmission in non-smokers but not in smokers who are already at higher risk. Future studies should determine whether better metabolic monitoring and treatment can reduce readmission risk.

AbstractBackground To distinguish the metabolic profile between women with diminished ovarian reserve (DOR) and those with normal ovarian reserve (NOR).Methods In this retrospective study, we enrolled 524 women under the age of 40 who were experiencing infertility: 261 in the DOR group and 263 in the NOR group. Physical characteristics and metabolic parameters were compared between these two groups.Results Women with DOR exhibited a higher propensity for elevated parameters including body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), as well as heightened serum levels of homocysteine (Hcy), triglycerides (TG), low-density lipoprotein (LDL), and triglyceride-glucose (TyG) index, while concurrently experiencing reduced serum levels of high-density lipoprotein (HDL) (P

Background: Neuregulin_4 (NRG4) is one of the adipokines members that synthesize adipose tissues. It has an activating effect on epidermal growth factor receptors (ErbB receptors). NRG4 has indirect effects on the hormonal environment through its interaction to ErbB receptors. Increased insulin resistance and chronic low-grade inflammation may be present when NRG4 levels are high in PCOS. Obesity and polycystic ovarian syndrome have recently gained a lot of attention. However, the literature on the connection between NRG4 and the PCOS phenotype is limited. Thus, this research aimed to identify neuregulin_4's function as a biomarker for insulin resistance in PCOS phenotypes. Methods: A case-control study and included 140 female cases effect by different phenotypes of PCOS. Patients samples were collected at the reproductive fertility consultant of the Teaching Hospital for Obstetrics and Gynecology, Kerbala health directorate, Iraq. The outpatient clinic serum hormonal levels and insulin concentration were determined by the electrochemiluminescence immunoassay "ECLIA" system. Elisa system was used for the detection of Neuregulin-4 protein level. Results: At the early age of participant NRG4 was increased significantly in all phenotypes of PCOS compared to control with a P< 0.05. interestingly, phenotype A was shown high level of NRG4 following phenotype C than phenotype D and phenotype B. Receiver Operator Characteristic Curves (ROC) analysis for NRG4 was performed and showed good diagnostic performers to word phenotype A. Conclusion: Females with phenotype A have a higher level of NRG4 than other phenotypes, which could be attributable to the more pronounced metabolic abnormalities in this phenotype. [ABSTRACT FROM AUTHOR]

(1) Vitamin D deficiency and changes in the endocrine system may stimulate systemic inflammation. VDR expression and the vitamin D concentration decrease with age, which is important in postmenopausal women for whom estrogen deficiency causes rapid bone loss. This group is, moreover, particularly at risk of developing atherosclerosis and its adverse consequences, such as chronic inflammation. The aim of this study was to assess the differentiation by the VDR genotype of the risk factors for so-called chronic low-grade inflammation and metabolic disorders. (2) We studied the differences between the anthropometric, metabolic, and inflammation parameters of VDR genotypes for Apa-I, Bsm-I, Fok-I, and Taq-I in a sample of 321 women aged 50–60 from an ethnically homogeneous urban population in Poland. (3) The TT Taq-I genotype presented a significantly higher rate of insulin resistance (HOMA) and lower serum levels of adiponectin than the other two genotypes. The AA genotype of the Bsm-I polymorphism was associated with a more atherogenic serum profile and significantly higher LDL and LDL/HDL values and Castelli Index. (4) Chronic low-grade inflammation was associated with the TT Taq-I genotype and presented a higher rate of insulin resistance. The AA genotype of the Bsm-I polymorphism presented a more atherogenic serum lipid profile and, therefore, a higher risk of developing cardiovascular disease. [ABSTRACT FROM AUTHOR]

Abstract Aims The aim of this study was to characterize the metabolites associated with small- and large-gestational-age newborns in maternal and cord blood, and to investigate potential mechanisms underlying the association between birthweight and metabolic disturbances. Research design and methods We recorded detailed anthropometric data of mother-offspring dyads. Untargeted metabolomic assays were performed on 67 pairs of cord blood and maternal fasting plasma samples including 16 pairs of small-for-gestational (SGA, 90th percentile) dyads. The association of metabolites with newborn birthweight was conducted to screen for metabolites with U-shaped and line-shaped distributions. The association of metabolites with maternal and fetal phenotypes was also performed. Results We found 2 types of metabolites that changed in different patterns according to newborn birthweight. One type of metabolite exhibited a “U-shaped” trend of abundance fluctuation in the SGA-AGA-LGA groups. The results demonstrated that cuminaldehyde level was lower in the SGA and LGA groups, and its abundance in cord blood was negatively correlated with maternal BMI (r = -0.352 p = 0.009) and weight gain (r = -0.267 p = 0.043). 2-Methoxy-estradiol-17b 3-glucuronide, which showed enrichment in the SGA and LGA groups, was positively correlated with homocysteine (r = 0.44, p

Due to the massive application of cypermethrin (CYP) for pest control in China, the adverse effects on non-target organisms have aroused great attention. However, comparative studies between its different stereoisomers remain scarce, especially for metabolism perturbations. Herein, the rats were administered α-CYP, β-CYP, and θ-CYP by gavage at doses of 8.5, 29.2, and 25.0 mg/kg/day, respectively, for 28 consecutive days. By blood examination, significant changes in liver and renal function parameters were observed in rats exposed to all three CYPs. The stereoisomeric selectivity in metabolic disturbances was assessed based on a metabolomic strategy via multivariate analysis and pathway analysis. The results demonstrated that amino acid and glycolipid metabolism were disrupted in all CYP groups. Among them, the most significant changes in the metabolic phenotype were observed in the θ-CYP group, with 56 differential metabolites enriched in 9 differential metabolic pathways. At the same time, the endogenous metabolite trimethylamine oxide (TMAO), which is closely linked to the gut microbiota, was also significantly elevated in this group. Gender differences were found in α- and θ-CYP-exposed rats, with perturbations in amino acid and glucose metabolism of greater concern in females and lipid metabolism of greater concern in males. Overall, β-CYP exhibited a lower risk of metabolic perturbations than α-CYP or θ-CYP, which helps to screen suitable agrochemical products for green agricultural development. [ABSTRACT FROM AUTHOR]

Aims: Thyroid dysfunction and metabolic disturbances are common in major depressive disorder (MDD) patients. We aimed to assess the relationship between thyroid dysfunction, metabolic disturbances, and clinical symptoms in Chinese first-episode, drug-naïve (FEDN) MDD patients using undirected and Bayesian network methods. Methods: 1718 FEDN MDD patients were recruited. Serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), thyroid peroxidases antibody (TPOAb), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and glucose were assessed. Blood pressure and body mass index were measured. Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety, and positive subscale of Positive And Negative Syndrome Scales were used to detect clinical symptoms. An undirected network with EBICglasso default and a directed acyclic graph (DAG) using the Bayesian network approach was conducted. Results: The prevalence rates of clinical symptoms, thyroid dysfunction, and metabolic dysfunction were as follows: anxiety (n=894, 52%), psychotic symptoms (171, 10%), subclinical hypothyroidism (SCH, n=1041, 61%), abnormal TgAb (n=297, 17%), abnormal TPOAb (n=438, 25%), hyperthyroidism (n=5, 0.3%), hypothyroidism (n=3, 0.2%), hyperglycemia (n=241, 14%), hypertriglyceridemia (n=668, 39%), low HDL-C (n=429, 25%), hypercholesterolemia (421, 25%), abnormal TC (357, 21%), abnormal LDL-C (185, 11%). overweight or obesity (n=1026, 60%), and hypertension (n=92, 5.4%). Both networks demonstrated serum TSH and TC levels and the severity of depression played an important role in the pathophysiology of MDD. Conclusions: MDD patients may have thyroid and metabolic dysfunction in the early stage. Targeting hypercholesterolemia, depressive symptoms, and SCH in MDD patients may hold promise in reducing clinical symptoms, metabolic disturbances, and thyroid dysfunction. abnormal TC (357, 21%), abnormal LDL-C (185, 11%). overweight or obesity (n=1026, 60%), and hypertension (n=92, 5.4%). Both networks demonstrated serum TSH and TC levels and the severity of depression played an important role in the pathophysiology of MDD. Conclusions: MDD patients may have thyroid and metabolic dysfunction in the early stage. Targeting hypercholesterolemia, depressive symptoms, and SCH in MDD patients may hold promise in reducing clinical symptoms, metabolic disturbances, and thyroid dysfunction. [ABSTRACT FROM AUTHOR]

Backgrounds: Co-occurrence of thyroid dysfunction, metabolic disturbances, and worsening clinical symptoms in major depressive disorder (MDD) patients with suicidal attempts (SA) are common. However, their relationship in SA patients remains unexplored. We aimed to (1) determine the independent association of thyroid dysfunction, clinical symptoms, and metabolic disturbances with SA; and (2) identify their interactions in SA patients via the network approach. Methods: 1718 FEDN MDD patients were recruited. Depressive, anxiety, and psychotic symptoms were assessed by the Hamilton Rating Scale for Depression (HAMD), the Hamilton Rating Scale for Anxiety (HAMA), and the Positive and Negative Syndrome Subscale positive subscale, respectively. The serumlevels of thyroid hormones and other metabolic parameters were assessed. Logistic regression model was applied to determine the correlates of SA. Network analysis was applied to determine the interaction between thyroid dysfunction, clinical symptoms, andmetabolic disturbances. Results: SA patients had significant worse metabolic disturbances, thyroid dysfunction, and clinical symptoms than non-SA patients. Thyroid peroxidases antibody, thyroid stimulating hormone (TSH), HAMD scores, HAMA scores, and systolic blood pressure was independently associated with SA. Network analysis suggested that TSH was the hub of the network, exhibiting substantial associations with metabolic disturbances, anxiety, and psychotic symptoms in SA patients. Conclusions: Our work highlights the predominant role of serum TSH levels in the pathophysiology of SA. Regular thyroid function tests might help early detect SA. Targeting increased TSH levels may help reduce metabolic disturbances and clinical symptoms in SA patients. [ABSTRACT FROM AUTHOR]

To distinguish the metabolic profile between women with diminished ovarian reserve (DOR) and those with normal ovarian reserve (NOR). In this retrospective study, we enrolled 524 women under the age of 40 who were experiencing infertility: 261 in the DOR group and 263 in the NOR group. Physical characteristics and metabolic parameters were compared between these two groups. Women with DOR exhibited a higher propensity for elevated parameters including body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), as well as heightened serum levels of homocysteine (Hcy), triglycerides (TG), low-density lipoprotein (LDL), and triglyceride-glucose (TyG) index, while concurrently experiencing reduced serum levels of high-density lipoprotein (HDL) (P < 0.05). Furthermore, the incidence rates of TG ≥ 1.7 mmol/L, hyperhomocysteinemia (HHcy), BMI ≥ 25 kg/m2, SBP/DBP ≥ 130/85 mmHg, and metabolic syndrome (MS) were significantly elevated within the DOR group as compared to the NOR group (P < 0.05). The prevalence of metabolic disturbances and HHcy were notably elevated in women with infertility and DOR compared to those with NOR. This study focused on the metabolic condition of women who had difficulty getting pregnant and had a decreased ovarian reserve. The findings indicated that these women had a higher likelihood of glucose and lipid metabolic disorders and elevated serum homocysteine levels compared to those with a normal ovarian reserve. These metabolic issues and elevated serum homocysteine levels were associated with an increased risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Obesity and overnutrition induce inflammation, leptin-, and insulin resistance in the hypothalamus. The mediobasal hypothalamus responds to exercise enabling critical adaptions at molecular and cellular level that positively impact local inflammation. This review discusses the positive effect of exercise on obesity-induced hypothalamic dysfunction, highlighting the mechanistic aspects related to the anti-inflammatory effects of exercise. In HFD-fed animals, both acute and chronic moderate-intensity exercise mitigate microgliosis and lower inflammation in the arcuate nucleus (ARC). Notably, this associates with restored leptin sensitivity and lower food intake. Exercise-induced cytokines IL-6 and IL-10 mediate part of these positive effect on the ARC in obese animals. The reduction of obesity-associated pro-inflammatory mediators (e.g., FFAs, TNFα, resistin, and AGEs), and the improvement in the gut–brain axis represent alternative paths through which regular exercise can mitigate hypothalamic inflammation. These findings suggest that the regular practice of exercise can restore a proper functionality in the hypothalamus in obesity. Further analysis investigating the crosstalk muscle–hypothalamus would help toward a deeper comprehension of the subject. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to characterize the metabolites associated with small- and large-gestational-age newborns in maternal and cord blood, and to investigate potential mechanisms underlying the association between birthweight and metabolic disturbances. Research design and methods: We recorded detailed anthropometric data of mother-offspring dyads. Untargeted metabolomic assays were performed on 67 pairs of cord blood and maternal fasting plasma samples including 16 pairs of small-for-gestational (SGA, < 10th percentile) dyads, 28 pairs of appropriate-for-gestational (AGA, approximate 50 percentile) dyads, and 23 pairs of large-for-gestational (LGA, > 90th percentile) dyads. The association of metabolites with newborn birthweight was conducted to screen for metabolites with U-shaped and line-shaped distributions. The association of metabolites with maternal and fetal phenotypes was also performed. Results: We found 2 types of metabolites that changed in different patterns according to newborn birthweight. One type of metabolite exhibited a "U-shaped" trend of abundance fluctuation in the SGA-AGA-LGA groups. The results demonstrated that cuminaldehyde level was lower in the SGA and LGA groups, and its abundance in cord blood was negatively correlated with maternal BMI (r = -0.352 p = 0.009) and weight gain (r = -0.267 p = 0.043). 2-Methoxy-estradiol-17b 3-glucuronide, which showed enrichment in the SGA and LGA groups, was positively correlated with homocysteine (r = 0.44, p < 0.001) and free fatty acid (r = 0.42, p < 0.001) in maternal blood. Serotonin and 13(S)-HODE were the second type of metabolites, denoted as "line-shaped", which both showed increasing trends in the SGA-AGA-LGA groups in both maternal and cord blood and were both significantly positively correlated with maternal BMI before pregnancy. Moreover, cuminaldehyde, serotonin, 13(S)-HODE and some lipid metabolites showed a strong correlation between maternal and cord blood. Conclusions: These investigations demonstrate broad-scale metabolomic differences associated with newborn birthweight in both pregnant women and their newborns. The U-shaped metabolites associated with both the SGA and LGA groups might explain the U-shaped association between birthweight and metabolic dysregulation. The line-shaped metabolites might participate in intrauterine growth regulation. These observations might help to provide new insights into the insulin resistance and the risk of metabolic disturbance of SGA and LGA babies in adulthood and might identify potential new markers for adverse newborn outcomes in pregnant women. [ABSTRACT FROM AUTHOR]

Chien-Chih Chen,1,2 Toshiaki Nakano,3,4 Li-Wen Hsu,3,4 Chia Yi Chu,1 Kuang-Tzu Huang4,5 1Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Liver Transplantation Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanCorrespondence: Kuang-Tzu Huang, Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, DAPI Road Niaosong Dist, Kaohsiung, 833, Taiwan, Tel +886-7-731-7123 (Ext.8193), Email huangkt@cgmh.org.twBackground: Atypical antipsychotics such as olanzapine often cause metabolic side effects such as obesity and diabetes, leading to an increased risk of nonalcoholic fatty liver disease. The aim of the present study was to investigate the effects of olanzapine treatment on hepatic lipid metabolism and its possible relationship with adipose tissue status.Methods: Using a female rat model, we investigated the effects of chronic olanzapine administration on the regulation of carbohydrate and lipid metabolism including lipid biosynthesis, oxidation, efflux, and lipolysis in liver and adipose tissue.Results: The body weight, liver mass and visceral adiposity after olanzapine treatment (2 mg/kg) for five weeks were not significantly different compared with vehicle controls. The serum level of triglycerides was higher in the vehicle controls than in olanzapine-treated rats. Unexpectedly, olanzapine treatment did not reduce glucose tolerance in our model. The expression of functional thermogenic protein uncoupling protein 1 (UCP1) was increased in brown adipose tissue (BAT) of the olanzapine group. Additionally, olanzapine treatment also reduced adipose inflammation in white adipose tissue (WAT). The transcription factor sterol regulatory element-binding protein (SREBP)-1c, a key early regulator of lipogenesis, was downregulated following olanzapine treatment. The expression of genes related to the triglycerides synthesis apparatus in the liver was upregulated in the olanzapine group. Olanzapine treatment induced genes involved in PPAR-α signaling and mitochondrial fatty acid oxidation in response to increased ATGL-mediated lipolysis in the liver.Conclusion: Together, our findings suggest a complicated link between olanzapine therapy and metabolic disturbance and may garner interest in assessing the action of antipsychotic-induced metabolic disturbances.Keywords: atypical antipsychotics, olanzapine, metabolic disturbances, weight gain, lipogenesis, lipolysis

Background: The side effects of antipsychotics (APs), related to weight gain and metabolic disturbances, can contribute to the health burden of psychotic people. Objective: To explore a) the level of adherence to the Mediterranean Diet (MedDiet) and consumption of fermented foods by first episode of psychosis (FEPs) patients taking APs, in comparison to matched -for age and BMI- healthy controls (HCs), and b) the effect of this dietary pattern on the biochemical and metabolic profile of FEPs. Method: The study population consisted of 33 FEPs treated with APs for less than 5 years, with no history of other chronic diseases, and an equal number of HCs. The FEPs were classified into two subgroups, according to their AP medication, depending on the documented risk of weight gain. A validated questionnaire for the adherence to Mediterranean diet and a food frequency questionnaire for selected fermented foods were completed by FEPs and HC. Anthropometric data and blood measurements were recorded for all participants. Results and conclusions: The FEPs showed a relevant lower overall adherence to the MedDiet, but no differences in consumption of fermented foods. Type of antipsychotic therapy uncovered differences in platelet count, vitamin B12, HDL and glucose (p < 0.05) between the subgroups of FEPs and HCs, although no values were abnormal. The MedDiet score was found to act as a prognostic factor for abnormal glucose levels in FEPs treated with APs associated with weight gain (p = 0.04). These results need to be confirmed by observations after long term adherence to MedDiet.

Schizophrenia, Borderline personality disorder, Psychoeducational and family therapy, Cognitive behavior therapy, Metacognitive training, Metabolic disturbances, Early intervention, Relapse prevention Novel trends refer to pioneering psychoeducational groups in borderline personality disorder, cannabis patterns in first episodes and predictive capability for weight gain during treatment in a transdiagnostic sample. Keywords: Schizophrenia; Borderline personality disorder; Psychoeducational and family therapy; Cognitive behavior therapy; Metacognitive training; Metabolic disturbances; Early intervention; Relapse prevention EN Schizophrenia Borderline personality disorder Psychoeducational and family therapy Cognitive behavior therapy Metacognitive training Metabolic disturbances Early intervention Relapse prevention 761 763 3 06/06/23 20230601 NES 230601 This editorial reports from seven international working groups from the US and Europe as follow-up of the Eight Kraepelin Symposium in Munich, LMU, recruiting former and recently recruited ones. [Extracted from the article]

Scopoletin, a typical example of a coumarin compound, exists in several Artemisia species and other plant genera. However, the systemic metabolic effects induced by scopoletin remain unclear. In the present study, we evaluated the metabolic profiles in scopoletin-exposed zebrafish embryos using UHPLC-Q-Obitrap-HRMS combined with multivariate analysis. Compared with the control group, 33 metabolites in scopoletin group were significantly upregulated, while 27 metabolites were significantly downregulated. Importantly, scopoletin exposure affected metabolites mainly involved in phosphonate and phosphinate metabolism, vitamin B6 metabolism, histidine metabolism, sphingolipid metabolism, and folate biosynthesis. These results suggested that scopoletin exposure to zebrafish embryos exhibited marked metabolic disturbance. This study provides a perspective of metabolic impacts and the underlying mechanism associated with scopoletin exposure. [ABSTRACT FROM AUTHOR]

Covid-19 pandemic forced the governments to choose the policy to the lockdown the gathering centers­, including universities and schools to prevent the rapid spread of the disease, forcing millions of people to stay at home for several weeks and even more. Staying in the home for such long periods is associated with a change in the wake/sleep period (a kind of social jet lag) and the resulting alteration in feeding time and type of food. Moreover, the prevalence of anxiety and depression resulted from the reduction in physical activity and bad news also may help to worsen the social jetlag effect on these parts of society. Possible hazardous changes in this factor are reviewed in this study and some suggestions for better management of this condition are also offered. Pubmed, SCOPUS, WOS, and Google Scholar data banks were searched using the following keyword in combination and/or alone: jetlag, social jetlag, Chronobiology, photoperiod, metabolic disease, cardiovascular, sleep/weak period. Longtime lockdown gathering centers are shown to change the photoperiod cycle in people, and it may induce several consequences, including the effects on cognitive brain function, induce mental illness, metabolic syndrome, insulin resistance, mitochondrial aging, and cardiovascular diseases. Considering these facts, it is important to make rehabilitation programs for all the societies’ members for post-pandemic time.

(1) Vitamin D deficiency and changes in the endocrine system may stimulate systemic inflammation. VDR expression and the vitamin D concentration decrease with age, which is important in postmenopausal women for whom estrogen deficiency causes rapid bone loss. This group is, moreover, particularly at risk of developing atherosclerosis and its adverse consequences, such as chronic inflammation. The aim of this study was to assess the differentiation by the VDR genotype of the risk factors for so-called chronic low-grade inflammation and metabolic disorders. (2) We studied the differences between the anthropometric, metabolic, and inflammation parameters of VDR genotypes for Apa-I, Bsm-I, Fok-I, and Taq-I in a sample of 321 women aged 50–60 from an ethnically homogeneous urban population in Poland. (3) The TT Taq-I genotype presented a significantly higher rate of insulin resistance (HOMA) and lower serum levels of adiponectin than the other two genotypes. The AA genotype of the Bsm-I polymorphism was associated with a more atherogenic serum profile and significantly higher LDL and LDL/HDL values and Castelli Index. (4) Chronic low-grade inflammation was associated with the TT Taq-I genotype and presented a higher rate of insulin resistance. The AA genotype of the Bsm-I polymorphism presented a more atherogenic serum lipid profile and, therefore, a higher risk of developing cardiovascular disease.

Long-chain polyunsaturated fatty acids n-3 series (n-3 LC-PUFAs), especially eicosapentaenoic and docosahexaenoic acids, are known to exert preventive effects on obesity and metabolic syndrome. Mainly consumed in the form of fish oil, LC-PUFAs n-3 are also found in significant quantities in other sources such as certain microalgae. The aim of this study was to evaluate the effects of Diacronema lutheri (Dia), a microalga rich in n-3 LC-PUFAs, on metabolic disorders associated with obesity. Three groups of male Wistar rats (n = 6 per group) were submitted for eight weeks to a standard diet or high-fat and high-fructose diet (HF), supplemented or not with 12% of Dia (HF-Dia). Compared to HF rats, HF-Dia rats showed a 41% decrease in plasma triacylglycerol (TAG) and an increase in plasma cholesterol (+35%) as well as in high-density lipoprotein cholesterol (+51%) without change to low-density lipoprotein cholesterol levels. Although fasting glycemia did not change, glucose and insulin tolerance tests highlighted an improvement in glucose and insulin homeostasis. Dia supplementation restored body weight and fat mass, and decreased levels of liver TAG (−75%) and cholesterol (−84%). In HF-Dia rats, leptin was decreased (−30%) below the control level corresponding to a reduction of 68% compared to HF rats. Similarly, the anti-inflammatory cytokines interleukin-4 (IL-4) and IL-10 were restored up to control levels, corresponding to a 74% and 58% increase in HF rats, respectively. In contrast, the level of IL-6 remained similar in the HF and HF-Dia groups and about twice that of the control. In conclusion, these results indicated that the D. lutheri microalga may be beneficial for the prevention of weight gain and improvement in lipid and glucose homeostasis. [ABSTRACT FROM AUTHOR]

A considerable number of patients suffer from adverse metabolic reactions caused by atypical antipsychotics (AAPs), however, current management strategies are disappointing to clinicians. Preclinical studies have consistently demonstrated that intermittent fasting (IF) has robust disease-modifying efficacy in animal models in a wide range of pathological conditions, especially obesity and diabetes. However, it is unclear what role IF can play in addressing AAPs-induced metabolic disturbances. In our study, we found that a 5:2 IF regimen significantly ameliorated the metabolic disturbances induced by olanzapine (a drug representative of AAPs) in animal models. Meanwhile, our research suggests that IF altering food intake during the refeeding phase may account for the metabolic benefit. This study provides supporting evidence regarding a potentially cost-effective intervention strategy for AAPs-induced metabolic disturbances.

Introduction High BMI has been associated with psychiatric rehospitalisation. Objectives We aimed to replicate this finding in a large Swiss psychiatric cohort and to examine whether other metabolic disturbances are independently associated with psychiatric readmission. Methods Data on 16’727 hospitalizations of 7’786 patients admitted between January 1st, 2007 and December 31st, 2019 at the Department of Psychiatry of the Lausanne University Hospital, were collected. Metabolic syndrome was defined according to International Diabetes Federation definition. Generalized Linear Mixed Models were used to investigate the associations between psychiatric readmission and metabolic syndrome and/or its five components. Results The readmitted population (N=2’935; 37.7% patients) had higher BMI, and were more likely to have central obesity, hypertriglyceridemia, and hypertension. Multivariate analyses confirmed that having a BMI ≥ 25 kg.m-2 was associated with psychiatric readmission (25 kg.m-2≤ BMI< 30 kg.m-2: OR = 1.88; 95%CI [1.55-2.29]; BMI≥30 kg.m-2: OR = 3.5; 95%CI [2.85-4.30]) when compared to patients with 18.5≤BMI

Introduction Despite the huge progression in depression treatment, many individuals do not achieve full recovery. Studies demonstrated alternatives from neurotransmitter targets which are promising to predict and manage illness. Objectives This study aimed to select metabolic factors linked to the severity of depression symptoms. Methods 66 patients (36% males) with episode of depression from part of SANGUT study were assessed for laboratory biomarkers (insulin, glucose, ALT, AST, lipid profile, cortisol, hs-CRP), anthropometric measurements (BMI, body composition, WHR ratio) and severity of subjective depressive (BDI scale) and stress (PSS-10 scale) symptoms. Results Maximum accuracy for differentiating mood symptoms was achieved by the combination of triglycerides (cut-off point > 101 mg/dl) and HDL cholesterol (cut-off point 108.35 mg/dl) and hs-CRP (cut-off point

Background: The metabolic defect in glycogen storage disease type I (GSDI) results in fasting hypoglycemia and typical secondary metabolic abnormalities (eg, hypertriglyceridemia, hyperlactatemia, hyperuricemia). The aim of this study was to assess further perturbations of the metabolic network in GSDI patients under ongoing treatment. Methods: In this prospective observational study, plasma samples of 14 adult patients (11 GSDIa, 3 GSDIb. Mean age 26.4 years, range 16‐46 years) on standard treatment were compared to a cohort of 31 healthy controls utilizing ultra‐high performance liquid chromatography (UHPLC) in combination with high resolution tandem mass spectrometry (HR‐MS/MS) and subsequent statistical multivariate analysis. In addition, plasma fatty acid profiling was performed by GC/EI‐MS. Results: The metabolomic profile showed alterations of metabolites in different areas of the metabolic network in both GSD subtypes, including pathways of fuel metabolism and energy generation, lipids and fatty acids, amino acid and methyl‐group metabolism, the urea cycle, and purine/pyrimidine metabolism. These alterations were present despite adequate dietary treatment, did not correlate with plasma triglycerides or lactate, both parameters typically used to assess the quality of metabolic control in clinical practice, and were not related to the presence or absence of complications (ie, nephropathy or liver adenomas). Conclusion: The metabolic defect of GSDI has profound effects on a variety of metabolic pathways in addition to the known typical abnormalities. These alterations are present despite optimized dietary treatment, which may contribute to the risk of developing long‐term complications, an inherent problem of GSDI which appears to be only partly modified by current therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Parkinson’s disease (PD) is a prevalent neurological disease in the elderly with increasing morbidity and mortality. Despite enormous efforts, rapid and accurate diagnosis of PD is still compromised. Metabolomics defines the final readout of genome-environment interactions through the analysis of the entire metabolic profile in biological matrices. Recently, unbiased metabolic profiling of human sample has been initiated to identify novel PD metabolic biomarkers and dysfunctional metabolic pathways, however, it remains a challenge to define reliable biomarker(s) for clinical use. Methods We presented a comprehensive metabolic evaluation for identifying crucial metabolic disturbances in PD using liquid chromatography-high resolution mass spectrometry-based metabolomics approach. Plasma samples from 3 independent cohorts (n = 460, 223 PD, 169 healthy controls (HCs) and 68 PD-unrelated neurological disease controls) were collected for the characterization of metabolic changes resulted from PD, antiparkinsonian treatment and potential interferences of other diseases. Unbiased multivariate and univariate analyses were performed to determine the most promising metabolic signatures from all metabolomic datasets. Multiple linear regressions were applied to investigate the associations of metabolites with age, duration time and stage of PD. The combinational biomarker model established by binary logistic regression analysis was validated by 3 cohorts. Results A list of metabolites including amino acids, acylcarnitines, organic acids, steroids, amides, and lipids from human plasma of 3 cohorts were identified. Compared with HC, we observed significant reductions of fatty acids (FFAs) and caffeine metabolites, elevations of bile acids and microbiota-derived deleterious metabolites, and alterations in steroid hormones in drug-naïve PD. Additionally, we found that L-dopa treatment could affect plasma metabolome involved in phenylalanine and tyrosine metabolism and alleviate the elevations of bile acids in PD. Finally, a metabolite panel of 4 biomarker candidates, including FFA 10:0, FFA 12:0, indolelactic acid and phenylacetyl-glutamine was identified based on comprehensive discovery and validation workflow. This panel showed favorable discriminating power for PD. Conclusions This study may help improve our understanding of PD etiopathogenesis and facilitate target screening for therapeutic intervention. The metabolite panel identified in this study may provide novel approach for the clinical diagnosis of PD in the future.

Purpose: Fatty acids (FA), particularly polyunsaturated (PUFA) ones, are involved in the regulation of glycemic control, lipid metabolism, and inflammation. The aim of the study was to assess patient FA profile in relation to obesity, lipid and carbohydrate metabolism disturbances, and weight loss. Materials and Methods: The studied group consisted of 51 patients with extreme obesity, 23 of whom achieved radical weight reduction within 1 year after a laparoscopic sleeve gastrectomy (LSG). FA levels were determined using gas chromatography with flame ionization detection. Results: Patients with extreme obesity and higher serum PUFA content have lower serum levels of SFA and MUFA (especially myristic, palmitic, lignoceric acids and palmitoleic, oleic acids), as well as lower triglyceride and higher HDL-cholesterol concentrations and it was not influenced by CEPT Taq1B variant. At baseline, the fatty acid profile of patients with type II diabetes differ from patients with dyslipidemia. In patients who had lost weight, significantly lower levels of selected saturated FA and major trans-fatty acid, elaidic, were found. Moreover, the proportion of PUFA was increased. Conclusion: In extreme obesity, higher PUFA exert their favorable effects on serum lipids. Significant weight reduction after the bariatric surgery is associated with beneficial changes in the fatty acid profile. [ABSTRACT FROM AUTHOR]

Obesity and overnutrition induce inflammation, leptin-, and insulin resistance in the hypothalamus. The mediobasal hypothalamus responds to exercise enabling critical adaptions at molecular and cellular level that positively impact local inflammation. This review discusses the positive effect of exercise on obesity-induced hypothalamic dysfunction, highlighting the mechanistic aspects related to the anti-inflammatory effects of exercise. In HFD-fed animals, both acute and chronic moderate-intensity exercise mitigate microgliosis and lower inflammation in the arcuate nucleus (ARC). Notably, this associates with restored leptin sensitivity and lower food intake. Exercise-induced cytokines IL-6 and IL-10 mediate part of these positive effect on the ARC in obese animals. The reduction of obesity-associated pro-inflammatory mediators (e.g., FFAs, TNFα, resistin, and AGEs), and the improvement in the gut–brain axis represent alternative paths through which regular exercise can mitigate hypothalamic inflammation. These findings suggest that the regular practice of exercise can restore a proper functionality in the hypothalamus in obesity. Further analysis investigating the crosstalk muscle–hypothalamus would help toward a deeper comprehension of the subject.

Scopoletin, a typical example of a coumarin compound, exists in several Artemisia species and other plant genera. However, the systemic metabolic effects induced by scopoletin remain unclear. In the present study, we evaluated the metabolic profiles in scopoletin-exposed zebrafish embryos using UHPLC-Q-Obitrap-HRMS combined with multivariate analysis. Compared with the control group, 33 metabolites in scopoletin group were significantly upregulated, while 27 metabolites were significantly downregulated. Importantly, scopoletin exposure affected metabolites mainly involved in phosphonate and phosphinate metabolism, vitamin B6 metabolism, histidine metabolism, sphingolipid metabolism, and folate biosynthesis. These results suggested that scopoletin exposure to zebrafish embryos exhibited marked metabolic disturbance. This study provides a perspective of metabolic impacts and the underlying mechanism associated with scopoletin exposure.

ABSTRACT Objective: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. Subjects and methods: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. Results: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. Conclusion: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

Long-chain polyunsaturated fatty acids n-3 series (n-3 LC-PUFAs), especially eicosapentaenoic and docosahexaenoic acids, are known to exert preventive effects on obesity and metabolic syndrome. Mainly consumed in the form of fish oil, LC-PUFAs n-3 are also found in significant quantities in other sources such as certain microalgae. The aim of this study was to evaluate the effects of Diacronema lutheri (Dia), a microalga rich in n-3 LC-PUFAs, on metabolic disorders associated with obesity. Three groups of male Wistar rats (n = 6 per group) were submitted for eight weeks to a standard diet or high-fat and high-fructose diet (HF), supplemented or not with 12% of Dia (HF-Dia). Compared to HF rats, HF-Dia rats showed a 41% decrease in plasma triacylglycerol (TAG) and an increase in plasma cholesterol (+35%) as well as in high-density lipoprotein cholesterol (+51%) without change to low-density lipoprotein cholesterol levels. Although fasting glycemia did not change, glucose and insulin tolerance tests highlighted an improvement in glucose and insulin homeostasis. Dia supplementation restored body weight and fat mass, and decreased levels of liver TAG (−75%) and cholesterol (−84%). In HF-Dia rats, leptin was decreased (−30%) below the control level corresponding to a reduction of 68% compared to HF rats. Similarly, the anti-inflammatory cytokines interleukin-4 (IL-4) and IL-10 were restored up to control levels, corresponding to a 74% and 58% increase in HF rats, respectively. In contrast, the level of IL-6 remained similar in the HF and HF-Dia groups and about twice that of the control. In conclusion, these results indicated that the D. lutheri microalga may be beneficial for the prevention of weight gain and improvement in lipid and glucose homeostasis.

Tertiary hyperparathyroidism (HPT III) occurs when an excess of parathyroid hormone (PTH) is secreted by parathyroid glands, usually after longstanding secondary hyperparathyroidism. Some authorities reserve the term for secondary hyperparathyroidism that persists after successful renal transplantation. Long-standing chronic kidney disease (CKD) is associated with several metabolic disturbances that lead to increased secretion of PTH, including hyperphosphatemia, calcitriol deficiency, and hypocalcaemia. Hyperphosphatemia has a direct stimulatory effect on the parathyroid gland cell resulting in nodular hyperplasia and increased PTH secretion. Prolonged hypocalcaemia also causes parathyroid chief cell hyperplasia and excess PTH. After correction of the primary disorder CKD by renal transplant, the hypertrophied parathyroid tissue fails to resolute, enlarge over and continues to oversecrete PTH, despite serum calcium levels that are within the reference range or even elevated. They also may become resistant to calcimimetic treatment. The main indication for treatment is persistent hypercalcemia and/or an increased PTH, and the primary treatment is surgery. Three procedures are commonly performed: total parathyroidectomy with or without autotransplantation, subtotal parathyroidectomy, and limited parathyroidectomy. It is important to remove superior parts of thymus as well. The most appropriate surgical procedure, whether it be total, subtotal, or anything less than subtotal including “limited” or “focused” parathyroidectomies, continues to be unclear and controversial. Surgical complications are rare, and parathyroidectomy appears to be a safe and feasible treatment option for HPT III. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a prevalent neurological disease in the elderly with increasing morbidity and mortality. Despite enormous efforts, rapid and accurate diagnosis of PD is still compromised. Metabolomics defines the final readout of genome-environment interactions through the analysis of the entire metabolic profile in biological matrices. Recently, unbiased metabolic profiling of human sample has been initiated to identify novel PD metabolic biomarkers and dysfunctional metabolic pathways, however, it remains a challenge to define reliable biomarker(s) for clinical use. Methods: We presented a comprehensive metabolic evaluation for identifying crucial metabolic disturbances in PD using liquid chromatography-high resolution mass spectrometry-based metabolomics approach. Plasma samples from 3 independent cohorts (n = 460, 223 PD, 169 healthy controls (HCs) and 68 PD-unrelated neurological disease controls) were collected for the characterization of metabolic changes resulted from PD, antiparkinsonian treatment and potential interferences of other diseases. Unbiased multivariate and univariate analyses were performed to determine the most promising metabolic signatures from all metabolomic datasets. Multiple linear regressions were applied to investigate the associations of metabolites with age, duration time and stage of PD. The combinational biomarker model established by binary logistic regression analysis was validated by 3 cohorts. Results: A list of metabolites including amino acids, acylcarnitines, organic acids, steroids, amides, and lipids from human plasma of 3 cohorts were identified. Compared with HC, we observed significant reductions of fatty acids (FFAs) and caffeine metabolites, elevations of bile acids and microbiota-derived deleterious metabolites, and alterations in steroid hormones in drug-naïve PD. Additionally, we found that L-dopa treatment could affect plasma metabolome involved in phenylalanine and tyrosine metabolism and alleviate the elevations of bile acids in PD. Finally, a metabolite panel of 4 biomarker candidates, including FFA 10:0, FFA 12:0, indolelactic acid and phenylacetyl-glutamine was identified based on comprehensive discovery and validation workflow. This panel showed favorable discriminating power for PD. Conclusions: This study may help improve our understanding of PD etiopathogenesis and facilitate target screening for therapeutic intervention. The metabolite panel identified in this study may provide novel approach for the clinical diagnosis of PD in the future. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women at reproductive age, which is characterized by obesity, hyperandrogenemia, and insulin resistance (IR). This study aimed to investigate the vitamin D status, and analyze the relationship between vitamin D deficiency and metabolic risk factors in PCOS women in Shaanxi China.Methods: A cross-sectional study included 169 women diagnosed with PCOS and 114 control women without PCOS. The serum 25(OH)D and metabolic markers were measured. Vitamin D deficiency was defined as serum 25(OH)D concentration less than 20 ng/mL. The primary outcome was the difference in vitamin D status between the PCOS and control groups, the secondary outcomes were correlations between serum 25(OH)D concentration and metabolic risk factors in women with PCOS.Results: The serum 25(OH)D concentration was significantly lower in women with PCOS than in controls (P < 0.05), and the prevalence rates of 25(OH)D deficiency and insufficiency were significantly higher in women with PCOS than in controls (P < 0.05). The serum 25(OH)D concentration was significantly lower in PCOS women with obesity or IR than in women without obesity or IR (P < 0.05), and the prevalence of 25(OH)D deficiency in PCOS women with obesity or IR was significantly higher than in women without obesity or IR (P < 0.05). Serum 25(OH)D concentration was significantly negatively correlated with body mass index (BMI), waist-to-hip ratio (WHR), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP) (P < 0.05). In comparison, serum 25(OH)D concentration was significantly positively correlated with high-density lipoprotein cholesterol (HDL-C) (P < 0.05). Increased BMI and WHR, high levels of fasting insulin, HOMA-IR, total cholesterol, LDL-C and hs-CRP were regarded as risk factors, but high level of HDL-C was considered to be protective factor of vitamin D deficiency in PCOS women.Conclusions: Vitamin D deficiency is prevalent in PCOS women in Shaanxi China, especially in those with obesity and IR. The serum 25(OH)D level was correlated with metabolic risk factors in PCOS women. Multi-center randomized controlled trials with large sample sizes are needed to probe the metabolic effect of vitamin D supplementation in PCOS women.

In recent decades, the prevalence of hyperuricemia (HU) is increasing worldwide; the role of uric acid (UA) in the genesis of various metabolic disorders, cardiovascular diseases, and kidney disease is being discussed. There are very few investigations of the rate of HU and its role in the development of diseases in certain social groups, including in professional athletes.Objective: to estimate the prevalence of HU and its role in the genesis of various pathological conditions and metabolic disturbances in professional athletes.Patients and methods. A retrospective comparative one-stage study was conducted, for which 2148 athletes who met inclusion criteria were selected and examined in the Federal Research and Clinical Center for Sports Medicine and Rehabilitation, Federal Biomedical Agency, in 2015. A control group consisted of 99 ageand sex-matched healthy volunteers examined at the V.A. Nasonova Research Institute of Rheumatology in 2017. The analysis included a comparison of the rate of HU and other examined parameters in professional athletes and healthy volunteers. The examined parameters were separately compared in athletes with/without HU, followed by statistical processing of results.Results. HU was detected in 306 (14.2%) of the 2148 athletes, more often in men (n=253 (20%) than in women (n=53 (6%); (p

Antipsychotics are the main pharmaceutical agents in treatment of schizophrenia and other mental disorders. According to literature data up to 60% of patients with schizophrenia have antipsychotic-induced metabolic disturbances. The main objective of pharmacogenetic studies is search for predictors of the response to therapy and definition of likelihood of development of undesirable phenomena. The main findings in the field of pharmacogenetics of metabolic disturbances were analysed. Recently, significant progress in the field of pharmacogenetic research was made which confirmed results of the previous studies and revealed new candidate genes. Ambiguous results in pharmacogenetic studies may be a reflection of complexity of pathogenesis of antipsychotic-induced weight gain, an influence of a set of epigenetic factors on mechanisms of its development. All this complicates design of the studies directed at identification of the candidate genes participating in realization of metabolic disturbances during intake of neuroleptics. Improvement of pharmacogenetic studies will provide the best understanding of how these genes are associated with antipsychotic-induced metabolic disturbances. Inclusion of pharmacogenetic approach in clinical guidelines is necessary, but now it is complicated that is associated mainly with the insufficient level of validity of the genetic markers studied and their ethnic heterogeneity. Use of pharmacogenetic testing improves rational therapy and contributes to the most efficient and safe therapy.

The therapy with antipsychotic drugs (AD) of the first and second generations is accompanied by metabolic side effects. The papers of recent years have revealed both central (induction of resistance to the satiety hormone leptin, change in level of adiponectin suppressing glyconeogenesis and elevating sensitivity of cells to insulin) and peripheral (activation of system of sterol regulatory element-binding proteins (SREBPs), performing transcription of genes of cholesterol and fatty acid biosynthesis along with inhibition of late phases of synthesis of cholesterol as well as change in intracellular cholesterol transport) mechanisms of realization of antipsychotic-induced metabolic disturbances. The study of the interrelationship between emergence of metabolic disturbances under therapy with AD and changes in production of cytokines and other inflammation factors is promising. A part of such studies as well as studies of peripheral mechanisms of side effects of AD can by efficiently performed in vitro on the models of cultivated cells, first of all, hepatogenic ones.