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Objective: White adipose tissue (WAT) possesses the remarkable remodeling capacity, and maladaptation of this ability contributes to the development of obesity and associated comorbidities. Calsyntenin-3 (CLSTN3) is a transmembrane protein that promotes synapse development in brain. Even though this gene has been reported to be associated with adipose tissue, its role in the regulation of WAT function is unknown yet. We aim to further assess the expression pattern of CLSTN3 gene in human adipose tissue, and investigate its regulatory impact on WAT function., Methods: In our study, we observed the expression pattern of Clstn3/CLSTN3 gene in mouse and human WAT. Genetic association study and expression quantitative trait loci analysis were combined to identify the phenotypic effect of CLSTN3 gene variant in humans. This was followed by mouse experiments using adeno-associated virus-mediated human CLSTN3 overexpression in inguinal WAT. We investigated the effect of CLSTN3 on WAT function and overall metabolic homeostasis, as well as the possible underlying molecular mechanism., Results: We observed that CLSTN3 gene was routinely expressed in human WAT and predominantly enriched in adipocyte fraction. Furthermore, we identified that the variant rs7296261 in the CLSTN3 locus was associated with a high risk of obesity, and its risk allele was linked to an increase in CLSTN3 expression in human WAT. Overexpression of CLSTN3 in inguinal WAT of mice resulted in diet-induced local dysfunctional expansion, liver steatosis, and systemic metabolic deficiency. In vivo and ex vivo lipolysis assays demonstrated that CLSTN3 overexpression attenuated catecholamine-stimulated lipolysis. Mechanistically, CLSTN3 could interact with amyloid precursor protein (APP) in WAT and increase APP accumulation in mitochondria, which in turn impaired adipose mitochondrial function and promoted obesity., Conclusion: Taken together, we provide the evidence for a novel role of CLSTN3 in modulating WAT function, thereby reinforcing the fact that targeting CLSTN3 may be a potential approach for the treatment of obesity and associated metabolic diseases., (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Objectives: To find whether Laparoscopic Roux-en-Y gastric bypass (RYGB) surgery was cost effective compared to conventional medical management (CMM) in Chinese patients with type 2 Diabetes(T2D) and obesity with a body mass index (BMI) ≥27.5 kg/m 2 in four years., Methods: A total of 106 obese T2D individuals who underwent RYGB and 106 T2D patients treated with CMM were enrolled from three academic medical centers. Total health related costs, Glycated Hemoglobin A1c (A1C) and BMI was recorded. Cost-Utility Analysis (CUA) was used. Utility values according to results of A1c were obtained from published studies., Results: Improvements were observed in A1C (8.6% at baseline to 6.2% in the first year, p < 0.001) and BMI (30.7 kg/m 2 at baseline to 24.3 kg/m 2 in the first year, p < 0.001), and the effect lasted for 4 years after RYGB. In the CMM group, A1C fluctuated in four years. The health utility for RYGB group scores 3.756, whereas CMM group scores 3.594 in four years. The total healthcare costs decreased sharply from the second year after RYGB ($8,483 [¥52,596] in the first year to $672[¥4,164] in the second year, p < 0.001) and maintained for 3 years. In the CMM group, the total healthcare costs changed without significance. RYGB costs US$19,359 (¥125,836) per quality-adjusted life years (QALY) gained (incremental cost-utility ratio [ICUR]) compared to CMM, which was lower than a willingness-to-pay (WTP) of $20,277/QALY., Conclusions: Compared to CMM, RYGB is cost-effective for Chinese patients with type 2 diabetes and obesity 4 years after operation.

In obesity, adipocytes exhibit high metabolic activity accompanied by an increase in lipid mobilization. Recent findings indicate that autophagy plays an important role in metabolic homeostasis. However, the role of this process in adipocytes remains controversial. Therefore, we performed an overall analysis of the expression profiles of 322 lysosomal/autophagic genes in the omental adipose tissue of lean and obese individuals, and found that among 35 significantly differentially expressed genes, 34 genes were upregulated. A large number of lysosomal/autophagic genes also were upregulated in murine 3T3-L1 adipocytes challenged with tumor necrosis factor α (TNFα) (within 24 h), which is in accordance with increased autophagy flux in adipocytes. SQSTM1/p62, a selective autophagy receptor that recognizes and binds specifically to ubiquitinated proteins, is transcriptionally upregulated upon TNFα stimulation as well. Perilipin 1 (PLIN1), a crucial lipid droplet protein, can be ubiquitinated and interacts with SQSTM1 directly. Thus, TNFα-induced autophagy is a more selective process that signals through SQSTM1 and can selectively degrade PLIN1. Our study indicates that local proinflammatory cytokines in obese adipose tissue impair triglyceride storage via autophagy induction.

Background: Leptin has been shown to stimulate the hypothalamus-pituitary-thyroid (HPT) axis in vivo and vitro. Its role in thyroid axis regulation after weight loss induced by bariatric surgery is still unknown. The aim of this study was to evaluate the influence of leptin on weight loss and thyroid function variation induced by Roux-en-Y gastric bypass (RYGB) surgery in euthyroid individuals with obesity and type 2 diabetes mellitus (T2DM)., Methods: 65 Chinese individuals with obesity and T2DM who underwent RYGB, and 27 healthy volunteers were enrolled in this retrospective study. Participants were evaluated for changes in anthropometric parameters, metabolic indexes, thyroid function, and leptin levels before and 12 months after surgery., Results: After RYGB, all of these patients experienced significant weight reduction and improved glucose control. Metabolic parameters were significantly ameliorated after surgery compared with baseline. Thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) declined in parallel. Median (IQR) plasma leptin levels decreased from 33.7 ng/mL (17.9-63.1) to 10.3 ng/mL (4.0-18.5). Pearson correlation analysis showed that TSH was significantly positively correlated with body mass index, C-reactive protein (CRP), and leptin. Multiple stepwise linear regression indicated that leptin and CRP were independent factors affecting TSH. The β coefficients were 0.38 (p = 0.001) and 0.32 (p = 0.004), respectively. There was a significant positive correlation between ΔTSH and Δleptin (r = 0.33, p = 0.01)., Conclusion: Decreased or normalized TSH levels after weight loss induced by RYGB might be mediated by the decline in leptin. There could be cross talk between adipose tissue and the HPT axis., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Background: This study was conducted to evaluate the prevalence of iron-deficiency anemia (IDA) after Roux-en-Y gastric bypass (RYGB) in Chinese obese patients with type 2 diabetes (T2DM). Furthermore, we evaluate potential predicting factors for onset of IDA after RYGB., Methods: A total of 184 obese T2DM individuals who underwent RYGB were enrolled in the study. Patients were divided into three groups: male, premenopausal female, and postmenopausal female. Hematologic parameters were obtained prior to and after surgery on standardized time intervals up to 24 months postoperatively., Results: At baseline, 6.0 % of patients were anemic, with similar percentages of anemic patients in each group. The relative decrease in the mean hemoglobin (Hb) level was significantly more pronounced for premenopausal female than for postmenopausal female or male. The percentage of anemia in male group had increased to 15.2 and 17.0 % at 6 and 12 months, respectively, and then decreased to 4.5 % at 24-month visit. In postmenopausal female group, the percentages of anemia constantly increase to 34.0 % at 6-month follow-up. Then, it decreased gradually to 25.0 and 26.7 % at 12- and 24-month visits, respectively. In premenopausal female group, the anemia percentages dramatically increased to 62.5 % at 24-month follow-up. Multiple logistic regression indicated that lower serum ferritin level preoperative and female were associated with higher possibility to suffer IDA 2 years after RYGB., Conclusions: Iron-deficiency and IDA are extremely frequent after RYGB in Chinese obese patients with T2DM. Premenopausal female presents unexpectedly high incidence of IDA during the 2-year observation.

Background/aims: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4), an adipocytokine associated with obesity and insulin resistance., Methods: Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting., Results: Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells., Conclusion: These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects., (© 2015 S. Karger AG, Basel.)

Obesity is associated with increased risk of developing numerous adverse health conditions. Cathepsin k (CTSK) is highly expressed in adipose tissues of obese patients and animal models. Although CTSK has been demonstrated to promote adipocyte differentiation in 3T3-L1 cells, the effects of CTSK selective inhibitor (CKSI) on weight gain and insulin resistance have not been well examined. High-fat diet (HFD) induced obese male C57BL/6 mice were fed a diet with or without CKSI for 8 weeks. The HFD induced increase in adipose tissue weight gain, increase in homeostasis model assessment (HOMA) index as well as accumulation of large adipocytes. After CKSI treatment, all these effects were blunted compared with the HFD control group. A study of the mechanism demonstrated a role for CKSI in significantly down-regulating the expression of two key transcription factors, peroxisome proliferators-activated receptor-γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), which are markers of adipogenic differentiation. These results indicated that the CKSI possesses an anti-obesity effect, possibly involving the inhibition of adipocyte differentiation. CTSK is likely to be a new target of therapeutic intervention for the treatment of obesity.

Adipose tissue coordinates energy storage and expenditure is one of the important organisms for maintaining energy metabolic homeostasis. Aging or intracellular or external stimuli may induce senescence of adipose progenitor and stem cells as well as mature adipocytes, which are accompanied by immune cell infiltration, diminished lipid storage and lipolysis capacity in white adipose tissue and impaired thermogenesis in brown and beige adipose tissue. These ultimately trigger metabolic diseases such as obesity and type 2 diabetes. Interventions for aging of adipose tissue mainly include drug therapy, caloric restriction, and gene editing, but there is still a lack of mature therapeutic options. Therefore, cytological alterations of adipose tissue aging and its molecular mechanisms can help to comprehensively understand the dynamic changes of adipose tissue during the aging process, which may provide theoretical clues to explore the pathogenesis of aging-related metabolic diseases and develop clinical therapeutic targets.

Women with obesity and polycystic ovary syndrome (OPOS) are at high risk for infertility. However, the reproductive effects of metabolic surgery on women with infertility and OPOS have not been fully elucidated. We investigated the natural conception rates after metabolic surgery, and the variables associated with infertility in women with OPOS. Shanghai Sixth People's Hospital, Shanghai, China. This study included 72 women with infertility and OPOS who underwent metabolic surgery and were followed up for 4 years after surgery. Finally, 54 patients completed the study. Reproductive outcomes were assessed, along with changes in anthropometric parameters and metabolic indices before and 1 year after surgery (prepregnancy). Logistic regression analysis was used to identify variables influencing natural conception and delivery outcomes. After metabolic surgery, 35 patients (64.8%) became pregnant naturally, while 16 were still unable to conceive naturally. Preoperative body mass index (BMI) tended to be lower in the natural conception group than in the no natural conception group (38.9 ± 6.9 versus 43.6 ± 11.0 kg/m2, P =.070) and there were no significant differences in weight loss between the 2 groups after surgery. Logistic regression analysis showed that the BMI 1 year after surgery (prepregnancy) was an independent predictor of natural conception, and receiver operating characteristic analysis showed that a BMI of 27.0 kg/m2 was the optimal cutoff for predicting successful natural conception after surgery. Metabolic surgery can improve fertility in women with OPOS. Patients with a BMI < 27.0 kg/m2 1 year after surgery (prepregnancy) are more likely to become pregnant naturally and give birth. • Women with obesity and polycystic ovary syndrome are at high risk for infertility. • Metabolic surgery can improve fertility in women with obesity and polycystic ovary syndrome. • BMI 1 year after surgery (prepregnancy) is an independent indicator of natural conception after surgery. • Patients with a BMI < 27.0 kg/m2 1 year after surgery (prepregnancy) were more likely to have a natural conception and successful birth. [ABSTRACT FROM AUTHOR]

Introduction: We explored whether visceral fat accumulation mediates the development of hepatic steatosis in individuals living with overweight and obesity. Methods: This cross-sectional study enrolled 769 outpatients with overweight and obesity aged 18–65 years. The controlled attenuation parameter (CAP) was used to quantify the degree of hepatic steatosis. Visceral fat accumulation, represented by the visceral fat area (VFA), was measured using magnetic resonance imaging. The associations of body mass index (BMI), VFA, and CAP with each other were assessed by univariate analysis, multivariate linear regression, and mediation analysis, respectively. Results: Compared with women, male subjects had higher BMI, VFA, and CAP levels. In both sex, CAP was positively correlated with BMI and VFA by the univariate analysis. After adjusting for demographic and serum characteristics, the linear correlation coefficients between BMI and CAP were 1.738 (95% confidence interval (CI): 1.100, 2.377), 1.524 (95% CI: 0.798, 2.249), and 2.650 (95% CI: 1.292, 4.009) in all subjects, females, and males, respectively, while those between VFA and CAP were 0.190 (95% CI: 0.133, 0.247), 0.184 (95% CI: 0.117, 0.252), and 0.194 (95% CI: 0.086, 0.301). Mediation analysis showed that visceral fat accumulation contributed to 51.37%, 53.85%, and 26.51% of obesity-induced hepatic steatosis in the total, female, and male subjects, respectively. Conclusion: Visceral fat accumulation partially mediates obesity-induced hepatic steatosis in individuals with overweight and obesity, especially in women. More focus on visceral fat reduction is needed in individuals with obesity. [ABSTRACT FROM AUTHOR]

Objective: Visceral obesity, reflected by the amount of visceral adipose tissue (VAT), is associated with multiple chronic diseases and metabolic disorders. The visceral fat area (VFA), measured by MRI, is the 'gold standard' for diagnosis of visceral obesity. In this study, a simple model to predict VFA was constructed to facilitate the identification and monitoring of patients who are at high risk of visceral obesity. Methods: The 721 overweight and obese participants were divided into two groups according to sex, then randomly assigned to derivation and validation cohorts in a 1:2 ratio. Data from the derivation group were used to construct a multiple linear regression model; data from the validation group were used to verify the validity of the model. Results: The following prediction equations, applicable to both sexes, were developed based on age, waist circumference (WC) and neck circumference (NC) that exhibited strong correlations with the VFA: VFA=3.7×age+2.4×WC+5.5×NC-443.6 (R2 = 0.511, adjusted R2 = 0.481, for men) and VFA=2.8×age+1.7×WC+6.5×NC-367.3 (R2 = 0.442, adjusted R2 = 0.433, for women). The data demonstrated good fit for both sexes. A comparison of the predicted and actual VFA in the verification group confirmed the accuracy of the equations: for men, R2 = 0.489, adjusted R2 = 0.484 and intra-class correlation coefficient (ICC) = 0.653 (p < 0.001) and for women: R2 = 0.538, adjusted R2= 0.536 and ICC = 0.672 (p < 0.001). The actual and predicted VFAs also showed good agreement in a Bland-Altman plot, indicating the significant correlations of both equations with the actual VFA. Conclusions: Based on readily available anthropometric data, VFA prediction equations consisting of age, WC and NC were developed. The equations are robust, with good predictive power in both sexes; they provide ideal tools for the early detection of visceral obesity in Chinese overweight and obese individuals. [ABSTRACT FROM AUTHOR]

Bariatric surgery is an effective and therapeutic way for different metabolic diseases. It has become a focus of attention about the effects and molecular mechanisms to bone metabolism. We aim to assess the changes of bone mineral density (BMD) among Chinese obese individuals with type 2 diabetes who have undergone Roux-en-Y gastric bypass surgery (RYGB). Two ghrelin gene products, namely unacylated ghrelin (UAG) and obestatin, were evaluated the roles in this pathologic process. University-affiliated hospital, China. Thirty patients who had received RYGB were enrolled in the study. Changes in anthropometric parameters, metabolic indexes, and serum UAG and obestatin were assessed preoperatively, 6, 12, and 24 months postoperatively. BMD at lumbar spine (LS), femoral neck (FN), and total hip (TH) were identified. RYGB resulted in statistical reductions of BMD in 3 different skeletal parts. After the first 6 months, BMD began to reduce and maintained a declining trend until 24 months postoperatively. Comparing to baseline, the maximal reduction of BMD was as high as 10.28% in total hip. The plasma concentration of UAG increased after 6 months (51.61 ± 55.21 versus 71.95 ± 64.91 pg/mL; P <.01), as well as the serum obestatin level (1.65 ± 0.88 versus 1.71 ± 0.99 ng/mL; P >.05). Although there was a slight drop of both peptides in the first year, they were still above the baseline. Notably, in the second year, UAG and obestatin rose to their peak values, respectively (91.90 ± 77.11 pg/mL and 1.74 ± 1.09 ng/mL). There was a negative correlation between UAG and BMD in all sites. Multiple linear regression analysis showed that the UAG level was the independent parameter associated with BMD at baseline (FN: β = -.407, P =.012 and TH: β = -0.396, P =.030 respectively), as well as the changes of UAG that were independently related with reduction percentage of LS BMD after 24 months (β = -.379, P =.046). The reduction of BMD in obese Chinese with type 2 diabetes was observed after RYGB. The pronounced increase of serum UAG acts as an independent risk factor for the decrease of BMD. Both serum levels of obestatin and UAG increased and BMD decreased gradually after RYGB in Chinese patients with obesity and T2D. Fluctuation in UAG was associated with lower BMD independent traditional risk factors and the mechanisms responsible for these physiopathological changes. We might explore a new target and to develop effective drugs for bone metabolic abnormalities after bariatric surgery. [ABSTRACT FROM AUTHOR]

Background Obesity and type 2 diabetes (T2D) are recognized as risk factors for hypogonadism in males. Serum sex hormone profiles have not been assessed adequately in obese Chinese males with T2D who have undergone Roux-en-Y gastric bypass (RYGB). Objective This study was conducted to examine the changes in sex hormone profiles, anthropometric parameters, and metabolic indexes before and after RYGB. Setting University Hospital, China. Methods There were 45 obese males with T2D who had undergone RYGB enrolled in this retrospective study, focusing on anthropometric parameters, metabolic indexes, and sex hormone profiles before and after surgery. Results The baseline prevalence of hypogonadism (defined by total testosterone [TT] levels<8 nM) was 33.33%. After surgery, both the levels of TT and sex hormone-binding globulin increased, while the levels of estradiol decreased. However, the calculated free testosterone, follicle-stimulating hormone, and luteinizing hormone levels remained unchanged. Multiple linear regression analysis showed that the visceral fat area was the only significant and independent parameter associated with TT levels at baseline ( β = −.479, P = .001). After surgery, decreases in the visceral fat area continued to be negatively associated with increases in TT ( r = −.411, P = .024). Conclusion These preliminary results demonstrated that TT could be significantly increased in obese Chinese males with T2D after RYGB; this occurs in part via a reduction in adipose tissue, especially visceral fat. Therefore, RYGB might be a promising therapy to treat hypogonadism in obese men with T2D. [ABSTRACT FROM AUTHOR]

Background The impact of bariatric surgery on thyroid hormone levels is poorly understood. Objectives To investigate changes in serum-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) after Roux-en-Y gastric bypass (RYGB) in euthyroid patients with obesity and type 2 diabetes. Setting University Hospital, China. Methods Eighty-one euthyroid Chinese patients with obesity and type 2 diabetes who underwent RYGB, and 20 healthy volunteers were enrolled in this retrospective study. Participants were evaluated for changes in anthropometric parameters, metabolic indexes, FT4, and TSH at baseline and 6 months after surgery. Multiple linear regression analysis was used to identify factors that could predict changes in FT4 and TSH. Results Mean FT4 levels decreased from 16.26–14.59 pmol/L ( P <.01), while TSH levels decreased significantly (2.19±1.09 mIU/L versus 1.97±1.12 mIU/L, P = .027) 6 months postsurgery. Multiple linear regression analysis showed that the waist/hip ratio (β =−7.406, P = .031) and duration of diabetes (β =−.087, P = .009) were independent factors contributing to this decrease in FT4 levels. Moreover, changes in TSH levels were significantly and positively correlated with 2-hour postprandial blood glucose at patient baseline (β = .064, P < .01). Conclusions The present study is the first to show that both serum levels of FT4 and TSH decrease after RYGB in euthyroid patients with obesity and type 2 diabetes. Our results suggest that not only can RYGB improve metabolic abnormalities, but it may also alter the feedback regulation of the thyroid system. [ABSTRACT FROM AUTHOR]