Sex-specific association of circulating Isthmin-1 with isolated post-challenge hyperglycemia.

Introduction: To explore the distribution of Isthmin-1 (ISM1) level and its association with isolated post-challenge hyperglycemia (IPH). Methods: A total of 522 participants without a history of diabetes were invited to attend a standard 75g 2-h oral glucose tolerance test (OGTT), and 71 subjects were further invited for a 3-h oral minimal model test. Insulin sensitivity and ß-cell function were evaluated using both HOMA and estimated from OGTT. Circulating ISM1 levels were determined by a commercially available ELISA kit. Results: A total of 76 (14.6%) participants were diagnosed as IPH, accounting for 61.3% of the newly diagnosed diabetes. ISM1 levels were significantly higher in men than in women (1.74 ng/mL versus 0.88 ng/mL). The inverse correlation between ISM1 and ß-cell function and IPH was only significant in men. After multivariate adjustment, per unit increment in ISM1 was associated with 0.68-fold (95% CI: 0.49-0.90) reduced odds ratio (OR) of IPH in men. Compared to men with the lowest ISM1 levels, the adjusted OR of IPH with the highest ISM1 levels decreased by 73% (95% CI: 0.11-0.61). Moreover, incorporation of ISM1 into the New Chinese Diabetes Risk Score (NCDRS) model yielded a substantial improvement in net reclassification improvement of 58% (95% CI: 27%-89%) and integrated discrimination improvement of 6.4% (95% CI: 2.7%-10.2%) for IPH. Conclusions: ISM1 was significantly and independently associated with IPH, and serves as a feasible biomarker for the early identification of men with high risk of IPH.

The Plasma Levels of Protein Adiponectin (AdipoQ) and Meteorin-Like (Metrnl) in Newly Diagnosed Type 2 Diabetes Mellitus.

Purpose: This study aimed to measure the concentrations of the Adiponectin and Meteorin - Like (Metrnl) in newly diagnosed type 2 diabetes patients. Patients and Methods: A comparative cross-sectional study contained two groups: Group 1 (86 newly diagnosed diabetes mellitus type 2 patients) and group 2 (71 healthy persons). The plasma concentrations of Adiponectin and Metrnl were measured by Enzyme Link Immunosorbent Assay (ELISA). Results: The plasma level of Adiponectin of the newly diagnosed diabetes mellitus type 2 group and the healthy group were 1219.82 ng/mL (1132.43-2772.50) and 1187.25 ng/mL (1160.66-3807.50) respectively. The plasma level of Metrnl of two groups were 757.60 pg/mL (564.15-994.00) and 697.60 pg/mL (538.50-986.10) respectively. There were no significant difference between two groups. Metrnl had no correlation with glucose, HbA1c, lipid profile, BMI. Adiponectin had correlation with Metrnl and HDL-cholesterol. Adiponectin had no correlation to glucose, HbA1c, LDL-cholesterol, total cholesterol, triglyceride, BMI. People with the lower Adiponectin concentration had the higher risk of diabetes (OR=6.52; 95% CI: 2.43 -17.55). Conclusion: Adiponectin and Metrnl were not significantly different in newly diagnosed type 2 diabetes and healthy people. The lower concentration of Adiponectin might increase the risk of type 2 diabetes.

Chemerin influences blood lipid of aged male mice under high fat diet and exercise states through regulating the distribution and browning of white adipose tissue.

BACKGROUND: With aging, white adipose tissue (WAT) undergoes distribution change and browning inhibition, which could be attenuated by exercise. Adipokine chemerin exerts roles in the above changes of WAT, and our previous studies demonstrated the effect of decreased chemerin on exercise-induced improvement of glucose and lipid metabolism in high fat diet (HFD) feeding male mice, so this study is to clarify whether chemerin's effects on glucose and lipid metabolism are associated with the distribution and browning of WAT. METHODS: After diet and exercise interventions, body weight and adipose tissue contents in different depots of male mice were weighed, body composition and energy metabolism parameters were determined by Echo MRI Body Composition Analyzer and metabolic cage, respectively. The levels of serum adiponectin and leptin were detected by ELISA, and the protein levels of PGC-1α, UCP1, adiponectin and leptin in WAT were measured by Western blot. RESULTS: Chemerin knockout exacerbated HFD-induced weight gain, upregulated the increases of visceral and subcutaneous WAT (vWAT and sWAT, especial in sWAT), and inhibited WAT browning, but improved blood lipid. Exercise reduced the body weight and WAT distribution, increased sWAT browning and further improved blood lipid in aged HFD male mice, which were abrogated by chemerin knockout. Detrimental alterations of leptin, adiponectin and adiponectin/leptin ratio were discovered in the serum and WAT of aged HFD chemerin(-/-) mice; and exercise-induced beneficial changes in these adipokines were blocked by chemerin knockout. CONCLUSION: Chemerin influences blood lipid of aged male mice under HFD and exercise states through regulating the distribution and browning of WAT, which might be related to the changes of adiponectin, leptin and adiponectin/leptin ratio.

Are Meteorin-Like Peptide and Asprosin Important in the Diagnosis of Breast Tumors?

INTRODUCTION: Breast cancer (BC) is one of the most common and leading causes of death in women. Therefore, early and accurate diagnosis is vital. In this study, meteorin-like (METRNL) peptide and asprosin levels were examined in breast tissue in invasive ductal carcinoma (IDC) of the breast, and the roles of these molecules in the diagnosis of BC were investigated. METHODS: In this retrospective study, tissues from patients with BC in the Pathology Department Laboratory of Firat University Faculty of Medicine, Elazig, Turkey, were used. Samples from 30 patients were used. The control group consisted of healthy breast tissues from the same patients. The pathology group consisted of breast tissues with IDC from the same patients. Breast tissue samples from both groups were evaluated immunohistochemically for METRNL and asprosin. RESULTS: Statistically significant differences were observed between both groups in terms of METRNL and asprosin. It was observed that METRNL and asprosin immunoreactivities were higher in breast tissues with IDC than in healthy breast tissues (p<0.001). CONCLUSION: When the study results were evaluated, it was seen that there was a significant relationship between healthy breast tissues and the ones with IDC in terms of METRNL and asprosin. It is thought that both METRNL and asprosin may be really important in the future for the early diagnosis and treatment of BC.

Comparative Effects of Gymnema sylvestre and Berberine on Adipokines, Body Composition, and Metabolic Parameters in Obese Patients: A Randomized Study.

Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. METHODOLOGY: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. CONCLUSION: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.

Anti-obesogenic effect of lupin-derived protein hydrolysate through modulation of adiposopathy, insulin resistance and gut dysbiosis in a diet-induced obese mouse.

The prevalence of obesity is increasingly widespread, resembling a global epidemic. Lifestyle changes, such as consumption of high-energy-dense diets and physical inactivity, are major contributors to obesity. Common features of this metabolic pathology involve an imbalance in lipid and glucose homeostasis including dyslipidemia, insulin resistance and adipose tissue dysfunction. Moreover, the importance of the gut microbiota in the development and susceptibility to obesity has recently been highlighted. In recent years, new strategies based on the use of functional foods, in particular bioactive peptides, have been proposed to counteract obesity outcomes. In this context, the present study examines the effects of a lupin protein hydrolysate (LPH) on obesity, dyslipidemia and gut dysbiosis in mice fed a high-fat diet (HFD). After 12 weeks of LPH treatment, mice gained less weight and showed decreased adipose dysfunction compared to the HFD-fed group. HFD-induced dyslipidemia (increased triglycerides, cholesterol and LDL concentration) and insulin resistance were both counteracted by LPH consumption. Discriminant analysis differentially distributed LPH-treated mice compared to non-treated mice. HFD reduced gut ecological parameters, promoted the blooming of deleterious taxa and reduced the abundance of commensal members. Some of these changes were corrected in the LPH group. Finally, correlation analysis suggested that changes in this microbial population could be responsible for the improvement in obesity outcomes. In conclusion, this is the first study to show the effect of LPH on improving weight gain, adiposopathy and gut dysbiosis in the context of diet-induced obesity, pointing to the therapeutic potential of bioactive peptides in metabolic diseases.

Exploratory Mass Spectrometry of Cerebrospinal Fluid from Persons with Autopsy-Confirmed LATE-NC.

Common neuropathologies associated with dementia include Alzheimer's disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Biofluid proteomics provides a window into the pathobiology of dementia and the information from biofluid tests may help guide clinical management. Participants (n = 29) had been autopsied and had antemortem CSF draws in a longitudinal cohort of older adults at the University of Kentucky AD Research Center. Cases were designated as LATE-NC + if they had LATE-NC stage > 1 (n = 9); the remaining 20 cases were designated LATE-NC-. This convenience sample of CSF specimens was analyzed in two separate processes: From one group, aliquots were depleted of highly abundant proteins using affinity spin columns. Tryptic digests of sample proteins were subjected to liquid chromatographic separation and mass spectrometry. Relative quantification was performed using Sciex software. Peptides referent to a total of 949 proteins were identified in the samples depleted of abundant proteins, and 820 different proteins were identified in the non-depleted samples. When the Bonferroni/false-discovery statistical correction was applied to account for having made multiple comparison tests, only 4 proteins showed differential expression (LATE-NC + vs LATE-NC-) in the non-depleted samples (RBP4, MIF, IGHG3, and ITM2B). Post hoc western blots confirmed that RBP4 expression was higher in the LATE-NC + cases at the group level. In summary, an exploratory assessment of proteomes of autopsy-confirmed LATE-NC and non-LATE-NC CSF did not demonstrate a clear-cut proteomic fingerprint that distinguished the two groups. There was, however, an increase in RBP4 protein levels in CSF from LATE-NC cases.

Adiponectin and Glucocorticoids Modulate Risk for Preterm Birth: The Healthy Start Study.

PURPOSE: Adiponectin is a potent uterine tocolytic that decreases with gestational age, suggesting it could be a maternal metabolic quiescence factor. Maternal stress can influence preterm birth risk, and adiponectin levels may be stress-responsive. We characterized associations between adiponectin and glucocorticoids with preterm birth and modeled their predictive utility. We hypothesized maternal plasma adiponectin and cortisol are inversely related and lower adiponectin and higher cortisol associate with preterm birth. METHODS: We performed a nested case-control study using biobanked fasting maternal plasma. We included low-risk singleton pregnancies, and matched 1:3 (16 preterm, 46 term). We quantified total, high (HMW), and low molecular weight (LMW) adiponectin using ELISA. We validated an HPLC-MS/MS serum assay for use in plasma, to simultaneously measure cortisol, cortisone, and five related steroid hormones. We used linear/logistic regression to compare group means and machine learning for predictive modeling. RESULTS: The preterm group had lower mean LMW adiponectin (3.07 µg/mL vs. 3.81 µg/mL at 15w0d, P=0.045) and higher mean cortisone (34.4 ng/mL vs. 29.0 ng/mL at 15w0d, P=0.031). The preterm group had lower cortisol-to-cortisone and lower LMW adiponectin-to-cortisol ratios. We found HMW adiponectin, cortisol-to-cortisone ratio, cortisone, maternal height, age, and pre-pregnancy BMI most strongly predicted preterm birth (AUROC=0.8167). In secondary analyses, we assessed biomarker associations with maternal self-reported psychosocial stress. Lower perceived stress associated with a steeper change in cortisone in the term group. CONCLUSION: Overall, metabolic and stress biomarkers associated with preterm birth in this healthy cohort. We identify a possible mechanistic link between maternal stress and metabolism for pregnancy maintenance.

Correlation Between Body Mass Index and Periodontitis: A Clinical and Biochemical Analysis.

Introduction Obesity is the excessive deposition of body fat in relation to lean body mass. In this research, its relation to periodontitis has been analysed using clinical and biochemical parameters. The current study assessed the correlation between body mass index (BMI) and periodontitis using salivary visfatin levels. Materials and methods Sixty participants (33 males and 27 females) were categorised into three different groups according to BMI: group 1: normal weight (n=20); group 2: overweight (n=20); and group 3: obese (n=20). Clinical parameters such as probing pocket depth (PPD) and clinical attachment level (CAL) were recorded. Salivary samples were collected and assessed for salivary visfatin levels with the aid of a human visfatin enzyme-linked immunosorbent assay (ELISA) kit. The results were assessed using IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, New York, United States). Results The PPD, CAL, and salivary visfatin levels were higher in group 3, followed by groups 2 and 1, and were statistically significant (p=0.000). The correlation between visfatin and PPD (r=0.962) and visfatin and CAL (r=0.978) was strongly positive and statistically significant. Conclusion This study demonstrates a strong positive correlation between BMI and periodontitis. Moreover, salivary visfatin can be considered a diagnostic marker for periodontal diseases.

Atg8/LC3 controls systemic nutrient surplus signaling in flies and humans.

Organisms experience constant nutritional flux. Mechanisms at the interface of opposing nutritional states-scarcity and surplus-enable organismal energy homeostasis. Contingent on nutritional stores, adipocytes secrete adipokines, such as the fat hormone leptin, to signal nutrient status to the central brain. Increased leptin secretion underlies metabolic dysregulation during common obesity, but the molecular mechanisms regulating leptin secretion from human adipocytes are poorly understood. Here, we report that Atg8/LC3 family proteins, best known for their role in autophagy during nutrient scarcity, play an evolutionarily conserved role during nutrient surplus by promoting adipokine secretion. We show that in a well-fed state, Atg8/LC3 promotes the secretion of the Drosophila functional leptin ortholog unpaired 2 (Upd2) and leptin from human adipocytes. Proteomic analyses reveal that LC3 directs leptin to a secretory pathway in human cells. We identified LC3-dependent extracellular vesicle (EV) loading and secretion (LDELS) as a required step for leptin release, highlighting a unique secretory route adopted by leptin in human adipocytes. In Drosophila, mutations to Upd2's Atg8 interaction motif (AIM) result in constitutive adipokine retention. Atg8-mediated Upd2 retention alters lipid storage and hunger response and rewires the bulk organismal transcriptome in a manner conducive to starvation survival. Thus, Atg8/LC3's bidirectional role in nutrient sensing-conveying nutrient surplus and responding to nutrient deprivation-enables organisms to manage nutrient flux effectively. We posit that decoding how bidirectional molecular switches-such as Atg8/LC3-operate at the nexus of nutritional scarcity and surplus will inform therapeutic strategies to tackle chronic metabolic disorders.

A quantitative pipeline to assess secretion of human leptin coding variants reveals mechanisms underlying leptin deficiencies.

The hormone leptin, primarily secreted by adipocytes, plays a crucial role in regulating whole-body energy homeostasis. Homozygous loss-of-function mutations in the leptin gene (LEP) cause hyperphagia and severe obesity, primarily through alterations in leptin's affinity for its receptor or changes in serum leptin concentrations. Although serum concentrations are influenced by various factors (e.g., gene expression, protein synthesis, stability in the serum), proper delivery of leptin from its site of synthesis in the endoplasmic reticulum via the secretory pathway to the extracellular serum is a critical step. However, the regulatory mechanisms and specific machinery involved in this trafficking route, particularly in the context of human LEP mutations, remain largely unexplored. We have employed the Retention Using Selective Hooks system to elucidate the secretory pathway of leptin. We have refined this system into a medium-throughput assay for examining the pathophysiology of a range of obesity-associated LEP variants. Our results reveal that leptin follows the default secretory pathway, with no additional regulatory steps identified prior to secretion. Through screening of leptin variants, we identified three mutations that lead to proteasomal degradation of leptin and one variant that significantly decreased leptin secretion, likely through aberrant disulfide bond formation. These observations have identified novel pathogenic effects of leptin variants, which can be informative for therapeutics and diagnostics. Finally, our novel quantitative screening platform can be adapted for other secreted proteins.

Balancing Act: Exploring the Gut Microbiota-Brown Adipose Tissue Axis in PCOS Pathogenesis and Therapeutic Frontiers.

Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.

Diagnostic and Prognostic Value of Serum Leptin in Critically Ill Patients with Acute versus Acute-on-Chronic Liver Failure.

Differentiation between acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) can be challenging in patients with de novo liver disease but is important to indicate the referral to a transplant center and urgency of organ allocation. Leptin, an adipocyte-derived cytokine that regulates energy storage and satiety, has multiple regulatory functions in the liver. We enrolled 160 critically ill patients with liver disease and 20 healthy individuals to measure serum leptin concentrations as a potential biomarker for diagnostic and prognostic purposes. Notably, patients with ALF had higher concentrations of serum leptin compared to patients with decompensated advanced chronic liver disease (dACLD) or ACLF (110 vs. 50 vs. 29 pg/mL, p < 0.001). Levels of serum leptin below 56 pg/mL excluded ALF in patients with acute hepatic disease, with a negative predictive value (NPV) of 98.8% in our cohort. Lastly, serum leptin did not show any dynamic changes within the first 48 h of ICU treatment, especially not in comparison with patients with ALF vs. ACLF or survivors vs. non-survivors. In conclusion, serum leptin may represent a helpful biomarker to exclude ALF in critically ill patients who present with acute liver dysfunction.

Effects of intermittent fasting combined with exercise on serum leptin and adiponectin in adults with or without obesity: a systematic review and meta-analysis of randomized clinical trials.

Context: Intermittent fasting (IF) and exercise training (Exe) have been evaluated in several studies for improving cardiometabolic biomarkers related to weight loss. However, further investigation is required to understand the potential effects on leptin and adiponectin concentrations. IF protocols have been shown to be efficient in improving adipokines, but further research is required to determine whether or not IF regimens combined with Exe are superior to Exe alone. Objective: The aim of this study was to determine whether or not interventions combining IF plus Exe are more effective than Exe only for improving serum leptin and adiponectin in adults with and without obesity. Data extraction: A systematic review and meta-analysis was performed by searching PubMed, Scopus, and Web of Science databases up to August 2023 for randomized clinical trials that determined the effects of IF plus Exe vs. Exe alone (control) on body weight, serum leptin, and serum adiponectin. Analyses were conducted for IF plus Exe vs. Exe alone to calculate weighted mean differences (WMD) and standardized mean differences (SMD). Analysis: The current meta-analysis included 6 studies with a total sample of 153 participants, with intervention durations ranging from three days to 52 weeks. IF plus Exe elicited significantly larger decreases in leptin levels [SMD = -0.47, p = 0.03], which were accompanied by weight loss [WMD = -1.25 kg, p = 0.05], as compared with exercise-only interventions, but adiponectin did not differ between the two [SMD = 0.02, p = 0.9]. Conclusion: IF combined with Exe reduced leptin significantly, but did not change adiponectin levels, when compared to exercise only. Perhaps these reductions in leptin levels may have been associated with weight loss; however, due to the small number of included studies and the high heterogeneity in the weight loss outcomes, this result is uncertain. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023460735.

Adipokine (adiponectin-rs1501299) Gene Variant and Patient Characteristics in Relation to Metabolic-associated Fatty Liver Disease.

Background: Several genetic and metabolic variables, most notably the variation in the adipokine gene rs1501298, have been linked to metabolic-associated fatty liver disease etiopathogenesis (MAFLD). Liver biopsy, the gold standard for diagnosing MAFLD, is an invasive procedure; therefore, alternative diagnostic methods are required. Consequently, the integration of these metabolic variables with some of the patients' characteristics may facilitate the development of noninvasive diagnostic methods that aid in the early detection of MAFLD, identification of at-risk individuals and planning of management strategies. Methods: This study included 224 Egyptians (107 healthy individuals and 117 MAFLD patients). Age, sex, BMI, clinical and laboratory characteristics, and rs1501299 adipokine gene polymorphisms were examined. The rs1501299 variant, insulin resistance, hypertension, obesity, blood pressure, lipid profile, hemoglobin A1C level, and hepatic fibrosis predictors were evaluated for MAFLD risk. The feasibility and effectiveness of developing non-invasive MAFLD diagnostic models will be investigated. Results: The +276G/T (rs1501299) polymorphism (GG vs GT/TT) was linked with MAFLD (OR: 0.43, CI: 0.26-0.69, P = 0.002). The GG variants had lower MAFLD rates than those of the GT and TT variants. In addition to altered lipid profiles, patients with MAFLD showed increased gamma-glutamyl transferase levels (GGT: 56 IU/L vs. 36 IU/L). Genetic diversity also affects the accuracy of hepatic fibrosis and steatosis prediction. Hepatic fibrosis and steatosis predictors had receiver operating characteristic (ROC) AUCs of 0.529%, 0.846%, and 0.700-0.825%, respectively. We examined a diagnostic model based on these variables and demonstrated its effectiveness. Conclusion: The Adipokine variant rs1501299 increased the risk of MAFLD. Identifying and genotyping this variation and other metabolic variables allow for a noninvasive diagnostic model for early MAFLD diagnosis and identification of those at risk. This study illuminates the prevention and management of MAFLD. Further research with more participants is needed to verify these models and to prove their MAFLD diagnostic efficacy.

Role of C1q/TNF-Related Protein 6 for the Evaluation of Coronary Heart Disease Associated with Type 2 Diabetes.

Objective: Coronary artery disease (CAD) and type 2 diabetes (T2DM) are closely associated with increased rate of death. C1q/TNF-related protein 6 (CTRP6) is a novel adipocytokine which plays an important role in glucose and lipid metabolism. Little is known about the function of CTRP6 in CAD and T2DM patients. Herein, we aimed to study the association of CTRP6 level with CAD and T2DM. Methods: This study included 51 CAD, 44 CAD+T2DM and 65 non-CAD+T2DM patients from Affiliated Aoyang Hospital of Jiangsu University. Serum CTRP6 concentrations were detected by ELISA. Multiple logistic regression was used to analyze the association of serum CTRP6 with CAD and T2DM. Results: Serum CTRP6 concentrations were significantly lower in CAD patients than controls. However, there is no significant statistical difference between CAD+T2DM patients and non-CAD+T2DM patients. Serum CTRP6 was negatively correlated with low-density lipoprotein cholesterol (LDL-C) (ρ=-0.2769, p=0.028) in controls. Serum CTRP6 was positively correlated with age (ρ=0.4121, p=0.0027), systolic blood pressure (SBP) (ρ=0.4012, p=0.0035), Creatinine (ρ=0.3295, p=0.0194), uric acid (UA) (ρ=0.3386, p=0.0162), and left ventricular end diastolic diameter (LVD) (ρ=0.4277, p=0.0042) and negatively correlated with ejection fraction (EF) (ρ=-0.3237, p=0.0342) in CAD patients. Serum CTRP6 was negatively correlated with high-density lipoprotein cholesterol (HDL-C) (ρ=-0.3164, p=0.0387) in CAD+T2DM patients. Multiple logistic regression showed that the decrease of CTRP6 was significantly related to the increased prevalence of CAD. What is more, CTRP6 increased prevalence of T2DM in CAD patients. Conclusion: Lower serum CTRP6 could be a risk factor of CAD. However, higher circulating CTRP6 associated with the increased prevalence of T2DM in CAD patients.

Chemerin Levels in Individuals with Type 2 Diabetes and a Normal Weight versus Individuals with Type 2 Diabetes and Obesity: An Observational, Cross-Sectional Study.

Chemerin acts as both a chemotactic agent and an adipokine that undergoes proteolytic cleavage, converting inactive precursors into their active forms before being subsequently inactivated. Elevated chemerin levels are linked to obesity and type 2 diabetes mellitus (T2D). This study aimed to elucidate the effects of T2D and obesity on chemerin levels by comparing plasma samples from individuals with a normal weight and T2D (BMI < 25; NWD group n = 22) with those from individuals who are overweight or obese and have T2D (BMI ≥ 25; OWD group n = 39). The total chemerin levels were similar in the NWD and OWD groups, suggesting that T2D may equalize the chemerin levels irrespective of obesity status. The cleavage of chemerin has been previously linked to myocardial infarction and stroke in NWD, with potential implications for inflammation and mortality. OWD plasma exhibited lower levels of cleaved chemerin than the NWD group, suggesting less inflammation in the OWD group. Here, we showed that the interaction between obesity and T2D leads to an equalization in the total chemerin levels. The cleaved chemerin levels and the associated inflammatory state, however, differ significantly, underscoring the complex relationship between chemerin, T2D, and obesity.

Adipokines measured during pregnancy and at birth are associated with infant negative affect.

BACKGROUND: Increased adiposity during pregnancy may be related to offspring risk for mental health disorders, although the biological mechanisms are poorly understood. One promising hypothesis is that factors secreted from adipocytes such as leptin and adiponectin may explain this association. The current study examined whether pregnancy or umbilical cord blood concentrations of leptin and/or adiponectin a) predict elevated infant negative affect at 6 months (an early life marker of risk for psychopathology); and b) help explain the association between pregnancy adiposity and increased infant negative affect. METHODS: Data came from a prospective cohort (N = 305) of pregnant individuals and their offspring. Second trimester adiposity was assessed using air displacement plethysmography. Concentrations of leptin and adiponectin were measured in second trimester plasma and umbilical cord plasma. Infant negative affect was assessed by standardized observation at 6 months. Second trimester inflammation was assessed using a comprehensive panel of cytokines. RESULTS: Lower second trimester adiponectin was associated with elevated infant negative affect, and mediated the effect of pregnancy adiposity on infant negative affect. This association was independent of the effect of second trimester inflammation. Umbilical cord leptin also predicted higher infant negative affect and mediated the association between pregnancy adiposity and infant negative affect. CONCLUSIONS: This is the first study to link pregnancy adiponectin or cord blood leptin to infant markers of risk for psychopathology, and the first to demonstrate that these adipokines mediate the association between pregnancy adiposity and offspring behavioral outcomes, suggesting novel markers of risk and potential mechanisms of effect.

Apelin-13 modulates the endometrial transcriptome of the domestic pig during implantation.

BACKGROUND: The peri-implantation period is a critical time during pregnancy that mostly defines the overall litter size. Most authors agree that the highest percentage of embryo mortality occurs during this time. Despite the brevity of the peri-implantation period, it is the most dynamic part of pregnancy in which the sequential and uninterrupted course of several processes is essential to the animal's reproductive success. Also then, the maternal uterine tissues undergo an intensive remodelling process, and their energy demand dramatically increases. It is believed that apelin, a member of the adipokine family, is involved in the control of female reproductive functions in response to the current metabolic state. The verified herein hypothesis assumed the modulatory effect of apelin on the endometrial tissue transcriptome on days 15 to 16 of gestation (beginning of implantation). RESULTS: The analysis of data obtained during RNA-seq (Illumina HiSeq2500) of endometrial slices treated and untreated with apelin (n = 4 per group) revealed changes in the expression of 68 genes (39 up-regulated and 29 down-regulated in the presence of apelin), assigned to 240 gene ontology terms. We also revealed changes in the frequency of alternative splicing events (397 cases), as well as single nucleotide variants (1,818 cases) in the presence of the adipokine. The identified genes were associated, among others, with the composition of the extracellular matrix, apoptosis, and angiogenesis. CONCLUSIONS: The obtained results indicate a potential role of apelin in the regulation of uterine tissue remodelling during the peri-implantation period.

Differential Modulation of Catecholamine and Adipokine Secretion by the Short Chain Fatty Acid Receptor FFAR3 and α2-Adrenergic Receptors in PC12 Cells.

Sympathetic nervous system (SNS) hyperactivity is mediated by elevated catecholamine (CA) secretion from the adrenal medulla, as well as enhanced norepinephrine (NE) release from peripheral sympathetic nerve terminals. Adrenal CA production from chromaffin cells is tightly regulated by sympatho-inhibitory α2-adrenergic (auto)receptors (ARs), which inhibit both epinephrine (Epi) and NE secretion via coupling to Gi/o proteins. α2-AR function is, in turn, regulated by G protein-coupled receptor (GPCR)-kinases (GRKs), especially GRK2, which phosphorylate and desensitize them, i.e., uncouple them from G proteins. On the other hand, the short-chain free fatty acid (SCFA) receptor (FFAR)-3, also known as GPR41, promotes NE release from sympathetic neurons via the Gi/o-derived free Gßγ-activated phospholipase C (PLC)-ß/Ca2+ signaling pathway. However, whether it exerts a similar effect in adrenal chromaffin cells is not known at present. In the present study, we examined the interplay of the sympatho-inhibitory α2A-AR and the sympatho-stimulatory FFAR3 in the regulation of CA secretion from rat adrenal chromaffin (pheochromocytoma) PC12 cells. We show that FFAR3 promotes CA secretion, similarly to what GRK2-dependent α2A-AR desensitization does. In addition, FFAR3 activation enhances the effect of the physiologic stimulus (acetylcholine) on CA secretion. Importantly, GRK2 blockade to restore α2A-AR function or the ketone body beta-hydroxybutyrate (BHB or 3-hydroxybutyrate), via FFAR3 antagonism, partially suppress CA production, when applied individually. When combined, however, CA secretion from PC12 cells is profoundly suppressed. Finally, propionate-activated FFAR3 induces leptin and adiponectin secretion from PC12 cells, two important adipokines known to be involved in tissue inflammation, and this effect of FFAR3 is fully blocked by the ketone BHB. In conclusion, SCFAs can promote CA and adipokine secretion from adrenal chromaffin cells via FFAR3 activation, but the metabolite/ketone body BHB can effectively inhibit this action.