Search

The effects of dulaglutide and a calorie-restricted diet (CRD) on visceral adipose tissue (VAT) and metabolic profiles in polycystic ovary syndrome (PCOS) have not been extensively investigated. In this study, we investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits as compared with a CRD regimen alone in overweight or obese PCOS-affected women. Between May 2021 and May 2022, this single-center, randomized, controlled, open-label clinical trial was conducted. Overall, 243 participants with PCOS were screened, of which 68 overweight or obese individuals were randomly randomized to undergo dulaglutide combined with CRD treatment (n = 35) or CRD treatment alone (n = 33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. As compared with the CRD group, the dulaglutide + CRD group had a considerably shorter median time to achieve 7% weight loss. There was no significant between-group difference in area change of VAT reduction (−0.97 cm2, 95% confidence interval from −14.36 to 12.42, p = 0.884). As compared with CRD alone, dulaglutide + CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. The results of the analyses showed different changes in menstruation frequency, additional metabolic profiles, hormonal markers, liver fat, and body composition between the two groups did not differ significantly. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These results emphasize the value of dietary intervention as the first line of treatment for PCOS-affected women, while glucagon-like peptide 1 receptor agonist therapy provides an efficient and typically well tolerated adjuvant therapy to aid in reaching weight targets based on dietary therapy in the population of overweight/obese PCOS-affected women.

To investigate the cross-sectional and longitudinal correlation between sex hormones and non-alcoholic fatty liver disease (NAFLD) in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG). A total of 360 patients with obesity aged 16–48 years (170 men and 190 women) were enrolled between May 2017 and March 2021. Among them, 132 patients (55 men and 77 women) who underwent LSG had follow-up data. Anthropometric parameters, metabolic variables, and sex hormones were measured. NAFLD was assessed by FibroScan with controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). In the preoperative cohort, levels of CAP and LSM were significantly higher in men than women. Lower total testosterone (TT) was associated with higher CAP and LSM in men, whereas higher TT was associated with higher CAP in women. In the postoperative cohort, TT levels and NAFLD were significantly modified after LSG in both genders. Changes in TT levels at 3 months after surgery were negatively correlated with changes in CAP levels in men, and changes in TT levels at 6 months after surgery were positively correlated with changes in CAP levels in women. After adjusting possible confounders, the changes in TT levels were independently correlated with CAP variation in both genders. LSG significantly modified TT levels and NAFLD in both genders. The correlation between TT levels and NAFLD at baseline as well as the changes after surgery suggested TT levels play an important role in the development and regression of NAFLD in both genders.

Diliqingna Dilimulati,&ast; Lei Du,&ast; Xiu Huang,&ast; Muthukumaran Jayachandran, Meili Cai, Yuqin Zhang, Donglei Zhou, Jiangfan Zhu, Lili Su, Manna Zhang, Shen Qu Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shen Qu; Manna Zhang, Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, 301 Middle Yanchang Road, Shanghai, 200072, People’s Republic of China, Tel +8602166301004 ; +8613774448495, Email qushencn@hotmail.com; mannazhang@126.comPurpose: Fibrinogen-like protein (FGL)-1 is an original hepatokine with a critical role in developing hepatic steatosis. This study intends to examine the pre- and postoperative serum FGL-1 levels in bariatric patients and identify its relationship with other clinical indicators.Patients and Methods: Ninety-two individuals (60 bariatric patients and 32 people with normal weight) were enrolled in this research between July 2018 and April 2021. All bariatric patients finished follow-up visits 6 months after laparoscopic sleeve gastrectomy (LSG). Clinical data, anthropometric parameters, biochemical variables, FibroScan, and serum FGL-1 levels were collected at baseline and 6 months after LSG.Results: FGL-1 levels in patients with obesity (44.66± 20.03 ng/mL) were higher than in individuals with normal weight (20.73± 9.73 ng/mL, p < 0.001). After LSG, FGL-1 levels were significantly decreased (27.53± 11.45 ng/mL, p < 0.001). Besides, body mass index (BMI), liver enzyme levels, glucose metabolism, lipid metabolism, uric acid (UA), controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) were significantly improved. After adjusting possible confounders, FGL-1 levels at baseline were negatively associated with changes in LSM levels; changes in FGL-1 levels showed positive correlations with changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and UA levels at 6 months after surgery.Conclusion: Serum FGL-1 levels were significantly decreased following LSG in patients with obesity. The preoperative serum FGL-1 levels could be a predictor of postoperative liver fibrosis improvement. Furthermore, the decreased FGL-1 levels were associated with improved liver enzymes and UA but not with bodyweight or glucolipid metabolism.Keywords: obesity, fibrinogen-like protein 1, liver fibrosis, laparoscopic sleeve gastrectomy

Background: Fibrinogen-like protein (FGL)-1 is a novel hepatokine that plays an important role in the development of hepatic steatosis and insulin resistance. The purpose of this study is to analyze serum FGL-1 levels in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG). Methods: Ninety-two individuals (32 people with normal weight and 60 patients with obesity) were included in this study. All patients with obesity finished follow-up visits at 6 months after LSG. Clinical data, anthropometric parameters and biochemical variables were collected. Serum FGL-1 levels were assessed by enzyme-linked immunosorbent assay (ELISA). Results: FGL-1 levels in patients with obesity (44.66 ± 20.03 ng/mL) were higher than individuals with normal weight (20.73 ± 9.73 ng/mL, P < 0.001). At baseline, FGL-1 levels were positively correlated with body mass index (BMI), blood pressure, hepatic enzyme levels, glucose metabolism, lipid metabolism and uric acid (UA). After LSG, FGL-1 levels were significantly decreased (27.53 ± 11.45 ng/mL, P < 0.001). Besides, BMI, hepatic enzyme levels, glucose metabolism, lipid metabolism and UA were significantly improved. After adjusting possible confounders, changes in FGL-1 levels at 6 months after surgery were positively correlated with changes in ALT, AST and UA levels.Conclusions: FGL-1 levels were closely correlated with various metabolic factors and decrease following LSG in patients with obesity. Furthermore, FGL-1 levels were more closely related to liver function and uric acid metabolism, but not body weight and glucolipid metabolism.Trial registration: This study protocol was approved by the Ethical Committee of Shanghai Tenth People’s Hospital. The Clinical Registration Number is ChiCTR-OCS-12002381. Date: 23 July 2012.

Objective Homo- or heterodimerization of G protein–coupled receptors (GPCRs) generally alters the normal functioning of these receptors and mediates their responses to a variety of physiological stimuli in vivo. It is well known that melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) are key regulators of appetite and energy homeostasis in the central nervous system (CNS). However, the GPCR partners of MC3R and MC4R are not well understood. Our objective is to analyze single cell RNA-seq datasets of the hypothalamus to explore and identify novel GPCR partners of MC3R and MC4R and examine the pharmacological effect on the downstream signal transduction and membrane translocation of melanocortin receptors. Methods We conducted an integrative analysis of multiple single cell RNA-seq datasets to reveal the expression pattern and correlation of GPCR families in the mouse hypothalamus. The emerging GPCRs with important metabolic functions were selected for cloning and co-immunoprecipitation validation. The positive GPCR partners were then tested for the pharmacological activation, competitive binding assay and surface translocation ELISA experiments. Results Based on the expression pattern of GPCRs and their function enrichment results, we narrowed down the range of potential GPCR interaction with MC3R and MC4R for further confirmation. Co-immunoprecipitation assay verified 23 and 32 novel GPCR partners that interacted with MC3R and MC4R in vitro. The presence of these GPCR partners exhibited different effects in the physiological regulation and signal transduction of MC3R and MC4R. Conclusions This work represented the first large-scale screen for the functional GPCR complex of central melanocortin receptors and defined a composite metabolic regulatory GPCR network of the hypothalamic nucleuses., Highlights • More GPCRs are found in the neurons than other cell types in the mouse hypothalamus, and their functions are significantly enriched in energy homeostasis and metabolism. • A total of 23 and 32 GPCRs are confirmed to be novel interacting partners of MC3R and MC4R in vitro, respectively. • The hetero-dimerization of identified GPCRs with MC3R and MC4R alters the signal transduction and surface translocation.

Objectives: To investigate the recovery of menses in polycystic ovary syndrome (PCOS) women with obesity after laparoscopic sleeve gastrectomy (LSG), and to explore the predictors for menstrual recovery. Methods: A total of 88 PCOS patients with obesity and 76 control patients with obesity aged 18-45 years were enrolled between May 2013 and December 2020. Preoperative clinical characteristics, metabolic parameters and sex hormones were collected. Postoperative menstrual status, body weight and use of oral contraceptives were obtained through telephone follow-up. Results: Patients with PCOS were followed up for at least six months after surgery, and the mean follow-up time was 3.23 years. About 24.66% of patients with PCOS started their first menstruation after LSG within 7 days, and 79.52% patients had regular menstruation at six months after LSG. In logistic regression analyses, duration of PCOS ≤4.5 years (P=0.007), number of preoperative menstruation per year >4.0 times/year (P=0.045), homeostatic model assessment of insulin resistance (HOMA-IR) ≤7.3 (P=0.020) and total testosterone (TT) ≤1.5 nmol/L (P=0.029) at baseline were significantly associated with menstrual resumption in PCOS patients within 6 months after LSG. After adjusting confounders, combination of four clinical indices at baseline could effectively predict menstrual recovery in PCOS patients within 6 months after LSG (AUC=0.837, [95%CI: 0.735-0.939], PConclusion: Overall, the combination of PCOS duration, menstruations per year, HOMA-IR and TT at baseline could be used as an effective tool for the prediction of menstrual recovery in PCOS patients within 6 months after LSG, which can be applied in preoperative evaluation.