Search

Gestational diabetes mellitus (GDM) is characterized by fasting hyperglycemia and glucose intolerance during pregnancy, but with poorly understood mechanisms. We found that prolactin receptor (Prlr) is markedly upregulated in liver of pregnant female mice. These findings have spurred the hypothesis that hepatic Prlr signaling is pivotal for physiological adaptation of hepatic metabolism to gestation. To address this hypothesis, we generated liver-conditional L-Prlr-KO mice, followed by determination of glucose and lipid metabolism in female L-Prlr-KO vs. age-matched female WT mice prior to and during gestation. Hepatic Prlr depletion did not impact glucose and lipid metabolism in virgin L-Prlr-KO mice. However, pregnant L-Prlr-KO mice developed GDM, as evidenced by the induction of glucose intolerance, fasting hyperglycemia, higher HOMA-IR levels and abnormal glucose-stimulated insulin secretion at gestational day 15.5. We reproduced these findings in female L-Prlr-KO mice in the 1st, 2nd and 3rd pregnancy, with the severity of GDM exacerbated by transient high fat feeding prior to conception in female L-Prlr-KO mice. Hepatic Prlr depletion did not affect litter size, but pups born to L-Prlr-KO mice had significantly lower birth weight. We recapitulated this finding in newborns derived from the 1st, 2nd and 3rd pregnancy in L-Prlr-KO mice. Hepatic Prlr depletion also resulted in increased triglyceride and cholesterol levels in liver, characteristic of nonalcoholic fatty liver disease and consistent with increased insulin resistance in pregnant L-Prlr-KO mice. Multiparous L-Prlr-KO mice developed postpartum prediabetes. Our studies unveiled an unprecedented role of hepatic Prlr signaling in regulating maternal hepatic metabolism to protect against GDM. Disclosure C. Zhu: None. J. Yamauchi: None. C. Pan: None. J. Gao: None. S. Qu: None. R.R. Banerjee: None. H. Dong: None. Funding National Key Research and Development Program of China (2018YFC1314100); National Natural Science Foundation of China (81970677)

Liver fatty acid-binding protein (FABP1) is associated with intracellular transportation of fatty acids. However, only few studies indicated the relationship between serum FABP1 and metabolism. This study aimed to investigate the association of FABP1 levels and metabolism factors, and its change with laparoscopic sleeve gastrectomy (LSG) in Chinese. The cross-sectional analysis included a total of 187 subjects, of which 65 were with normal weight (BMI 18-24 kg/m2), 59 with over weight (BMI25-27 kg/m2), and 64 with obesity (BMI≥28 kg/m2). We found FABP1 levels in obese (303±235pg/ml, p In conclusion, serum FABP1 were correlated with obesity and NAFLD, and it might be an important mediator participating in metabolism disorders. Disclosure H. You: None. Z. Lin: None. C. Zhu: None. X. Wen: None. M. Zhang: None. S. Qu: None. Funding National Key Research and Development Program of China (2018YFC1314101); National Natural Science Foundation of China (81700752, 81500687)

Objective: This study was designed to examine changes in body fat distribution after laparoscopic sleeve gastrectomy (LSG) and to confirm whether these changes are correlated with increased testosterone. Methods: A retrospective study was performed in 51 obese female patients with BMI 30-45 kg/m2 who underwent LSG from Shanghai Tenth People’s Hospital, 38 of whom were PCOS patients. The anthropometric indexes, sex hormone and ovarian volume of ultrasound examinations include both sides ovarian volume, mean ovarian volume (MOV) and maximal ovarian volume (MaxOV) were observed preoperative and follow-up at 3 and 6 months after LSG. The metabolic indexes and ovarian volume were compared before and after surgery. Results: Compared with preoperative, PCOS patients' weight, BMI, waist circumference and hip circumference were significantly lower at 3 and 6 months after operation (P Conclusions: TT and cFT decreased and SHBG increased significantly after LSG. MOV shrinked at 6 months after LSG and was no longer different from non-PCOS patients. LSG is not only an important treatment for weight loss, but also improve PCOS and its clinical symptoms effectively in severe obese women. Disclosure J. Gao: None. M. Zhang: None. C. Zhu: None. X. Wang: None. F. Mei: None. S. Qu: None. Funding National Natural Science Foundation of China (81601269)

Background: Hyperuricemia (HUA) and sex hormone imbalance in obese patients can be reversed by bariatric surgery. However, the relationships between changes in serum uric acid (SUA) and sex hormones variations after bariatric surgery is unexplored. We aimed to investigate the correlations between changes in SUA and sex hormones variations after laparoscopic sleeve gastrectomy (LSG) in Chinese obese patients in relation to gender. Methods: We enrolled 133 severely obese patients who underwent LSG in this study. SUA, sex hormones, and relevant metabolic parameters were compared pre- and 12 months post-LSG. Results: At baseline, HUA was more common in males than in females. Twelve months after LSG, significant improvements in BMI and glucolipid metabolic indices were noted. SUA levels and the prevalence of HUA were declined significantly in both gender while the changes in SUA and percentage of SUA variations were significantly greater in females than in males (all P Conclusion: LSG promotes more profound improvement of SUA levels in female obese patients than in males, and SUA reduction after surgery correlated significantly with different sex hormones changes in males and females. Disclosure C. Zhu: None. J. Gao: None. F. Mei: None. X. Wang: None. D. Zhou: None. S. Qu: None. Funding Shanghai Municipal Science and Technology Commission (17DZ1910603); Fundamental Research Funds for the Central Universities (1501219107); National Natural Science Foundation of China (81500650, 81700752, 81570782)

Objective: Obesity, a state of chronic low grade inflammation, has been reported to be associated with significant alterations of thyroid function. The purpose of this study is to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on thyroid function and its relation with inflammatory changes in severely obese patients. Methods: We performed a retrospective observational study of 128 severely obese patients (61.7% female; age 31.8 ± 10.0 years, BMI 39.4 ± 5.8 kg/m2) submitted to LSG. Patients were subdivided in two groups: euthyroid group and subclinical hypothyroidism (SCH) group. TSH, FT4, anthropometric data, and inflammatory markers were collected pre- and 1, 3, 6, and 12 months post-LSG. Results: The mean percent weight loss at 12 months was 37.2% ± 11.8%. The mean BMI decreased from 39.4 ± 5.8 kg/m2 to 27.1 ± 3.9 kg/m2. Patients with SCH (37.5% of patients) and higher TSH showed higher BMI, HOMA-IR, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) than those in euthyroid group (all P < 0.05). After surgery, TSH levels significantly decreased at 1, 3, 6, and 12 months regardless of thyroid function, which presented more apparent in SCH group. Additionally, we observed marked reduction of IL-6, IL-8, TNF-α, and CRP levels in SCH group, as well as IL-8, TNF-α, and CRP in euthyroid group from baseline by 12 months postoperatively. Moreover, decreased TSH levels correlated significantly with decreased BMI, HOMA-IR, IL-6, and TNF-α at 12 months after LSG. Conclusion: SCH in severely obesity subjects appears to be associated with excess weight, insulin resistance, and elevated inflammatory markers. LSG promotes a decrease of TSH that is significantly greater in patients with SCH, and associated with alleviation of inflammatory status in addition to substantial weight loss and improved insulin resistance after surgery. Disclosure C. Zhu: None. F. Mei: None. J. Gao: None. X. Wang: None. L. Li: None. L. Lu: None. D. Zhou: None. S. Qu: None.

Laparoscopic sleeve gastrectomy (LSG) has been proven successfully in weight reduction but with potential loss of bone mass. Previous studies indicate that bone morphogenetic protein 4 (BMP4) plays an important role both in bone formation and glucose-lipid metabolism. This study aimed to investigate the alteration of bone mineral density (BMD), bone metabolic parameters and serum BMP4 levels in Chinese obese subjects after LSG. Seventy-one obese patients (34 males, age 31.70±9.61 years and 37 females, age 32.80±11.45 years) were enrolled. BMD (at right hip, femoral neck and lumbar spine 1-4 (L1-L4) by dual-energy X-ray absorptiometry), bone metabolic markers and routine anthropometric/laboratory biochemical parameters at baseline, 3, 6 and 12 months after LSG (abbreviated as 3M/6M/12M Post-LSG) were recorded. Serum BMP4 levels were measured by enzyme-link immunosorbent assay. In females, BMD was significantly decreased at right hip at 3M/6M/12M Post-LSG, femoral neck at 6M/12M Post-LSG and L1-L4 at 6M Post-LSG (all P0.05). Intriguingly, serum BMP4 levels were reduced slightly at 3M Post-LSG (P=0.463), and significantly at 6M Post-LSG (from 75.51±16.54pg/ml to 65.40±10.51pg/ml, P=0.048) in females, while unchanged in males (all P>0.05). In all subjects, free calcium but not total calcium was increased at 12M Post-LSG (P=0.028). Vitamin D and 25(OH)VD were increased in males at 12M Post-LSG (all P In conclusion, the change of BMD differs between genders after LSG, significantly decreased in females while unchanged in males. Moreover, the decreased BMP4 levels may partly account for the diminished BMD in Chinese female obese subjects after LSG. Disclosure X. Wang: None. L. Li: None. C. Zhu: None. J. Gao: None. S. Qu: None.

Background: Acanthosis nigricans (AN) is a skin condition commonly often accompanied by insulin resistance and hyperinsulinemia. Patients with AN are prone to diabetes, especially in young obesity. Metformin were usually used to treat these patients. However, reports about the effectiveness of LSG surgery on young obese patients with AN are rare. Objective: The aim of our study was to evaluate the efficacy of LSG surgery on insulin secretion patterns and anthropometric variables for obese patients with AN. Methods: 30 young obese patients with AN were recruited for this study. Before and at 12 months after the LSG surgery, BMI and blood samples were collected. OGTT were used to evaluate the insulin level and its rhythm of secretion. AN extent and AN texture were determined according to the scale developed and validated. Results: For these patients, BMI decreased from 40.98±4.93 kg/m2 to 27.27±4.13 kg/m2 at 12 months after surgery. Along with weight loss, triglycerides and total cholesterol decreased significantly, and high-density lipoprotein cholesterol (HDL-C) increased significantly as of 12 months after surgery. But the change of low-density lipoprotein cholesterol (LDL-C) is not obvious. A significant decrease in insulin resistant (HOMA-IR) was observed. The insulin release curves showed hyperinsulinemia and abnormal rhythm of secretion before surgery. At 12 months after surgery the fasting, 2h postprandial insulin levels and the rhythm of insulin secretion were restored to normal level. But the insulin levels at 30min and 60min were higher than before surgery. The extent of AN for most patients were improved. Only 23.4% patients still were severe (vs. 59.3% before surgery). More than 50% patients were remission. Conclusion: In this study of LSG in obesity patients with AN, we found significant improvements in weight, dyslipidemia, hyperinsulinemia and AN extent. LSG will be a new effective therapeutic approach for young obesity patients with AN. Disclosure C. Qian: None. S. Qu: None. C. Zhu: None. J. Gao: None. F. Mei: None. L. Bu: None.

Background: Uric acid is believed be an important modulator in glucose and lipid metabolism. This study is aimed to estimate the efficacy of laparoscopic sleeve gastrectomy (LSG) on obese patients and find out the relationship of serum uric acid (SUA) to body fat distribution in both male and female of Chinese patients. Methods: A total of 65 obese patients (32 females and 33 males) who underwent LSG were enrolled for this study. Their body composition was measured by dual-energy X-ray absorptiometry (DEXA). The data of anthropometric measurements, glucolipid metabolism and SUA was collected before and 6 months after LSG separately. Results: More significant reduction of SUA was observed in the female group than the male group after LSG (female (17.98±12.72)% vs. male(3.22±15.66)%, p Conclusions: The efficacy of LSG on glycolipid metabolism may be associated with gender-related differences in body fat distribution. Uric acid may be a gendered modulator of glucose and lipid metabolism. Disclosure X. Zhang: None. F. Mei: None. J. Gao: None. X. Cheng: None. L. Bu: None. C. Zhu: None. S. Qu: None.

The aim of the study was to investigate the longitudinal bone mineral density(BMD) and bone metabolic related markers changes in obese patients with acanthosis nigricans (AN) and without AN(OB) after Laroscopic Sleeve Gastrectomy (LSG). 41 obese patients (AN group:n=29,OB group:n=12) were recruited in this study. Areal BMD (aBMD) and lumbar spine volumetric BMD (vBMD)were measured by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Insulin and markers of bone metabolism including 25-OHD, calcium, intact parathyroid hormone (iPTH), osteocalcin (OC), and type I collagen cross-linked C-terminal telopeptide (CTX) ] were assessed; Insulin area under the curve(AUCins) and HOMA-IR were computed. Results showed that the AN group had a higher fasting serum insulin (42.80±28.52 vs. 22.55±8.94mU/L,p=0.006), AUCins (522.42±280.32 vs. 263.87±195.75mU/L,p=0.008)and BMI(40.6±5.1 vs. 36.7±4.1kg/m2,p=0.024) compared to the OB group at baseline. The both groups did a obvious decrease in HOMA-IR after LSG; In AN group, there was a significant decrease in Lumbar vBMD(-4.4%,p=0.011), pelvic aBMD (-6.48%,p In conclusion, Insulin resistance was improved, and bone turnover was activated one year after LSG in both groups, but the bone loss was more likely to occur in the obese patients with acanthosis nigricans. Disclosure Y. Zhang: None. Z. Zhang: None. C. Zhu: None. S. Sun: None. Y. Yin: None. R. Cui: None. H. Sheng: None. S. Qu: None.

Background: Gut uses variety of pathways to establish closely contact with obesity and obesity related diabetes, including gut-brain cross-talk, gut microbiota, immune pathway and gastrointestinal hormones. In this study, we aimed to identify the key pathways and genes of gastric mucosa in obesity patients with or without type 2 diabetes. Methods: Our study was divided into three groups, healthy control group with normal BMI, patients with simple obesity(OB) and obesity with type 2 diabetes mellitus(OD), three cases in each groups. Gastric mucosal tissues were isolated then analyzed by gene microarray. The differentially expressed genes were screened by functional enrichment analysis and pathway analysis. Results: 262 up-regulated genes and 265 down-regulated genes were differentially expressed between OB and normal-BMI patients. Besides, 1756 up-regulated genes and 1053 down-regulated genes were differentially expressed between OD and control subjects (fold change>2 p < 0.05). For DEGs comparisons in each group, 13 genes were co-up regulated, 10 genes were co-down regulated, and an additional 12 genes showed different trends. After analyzing the biological process and molecule function of differential expression genes, these genes were found to play crucial roles mainly in cellular metabolic, protein binding and other biological process. The analysis of KEGG showed that the relevant genes participate in Citrate cycle, NF-kappa B and PI3K-Akt signaling pathway. Conclusions: During the process of obesity and obesity related diabetes, in gut there is not only one specific gene or pathway, but multiple genes and pathways that change. The effects of genes expressed in gastric mucosa mainly influence cellular metabolic processes, NF-kappa B and other proinflammatory signaling pathway. Disclosure X. Wen: None. Y. Zhang: None. R.J. Wu: None. C. Zhu: None. R. Cui: None. Y. Hui: None. F.Y. Mei: None. J. Gao: None. S. Qu: None. L. Bu: None.

Retinol binding protein 4 (RBP4) is implicated in the regulation of energy metabolism and insulin sensitivity. Laparoscopic sleeve gastrectomy (LSG) has been proven effectively in treating T2DM and other obesity-related comorbidities. We aimed to investigate the association between RBP4 with insulin resistance and the change of RPB4 levels after laparoscopic sleeve gastrectomy (LSG) in Chinese obese patients. Eighty-two obese patients (34 males and 48 females) were enrolled and 30 subjects (10 males and 20 females) underwent LSG in this study. Anthropometric and glucose metabolic parameters were measured. Serum RBP4 levels were detected by enzyme-link immunosorbent assay. In all subjects, serum RBP4 levels were positively associated with BMI, OGTT blood glucose at 0, 30, 120, 180mins, fasting insulin, fasting C-peptide and HOMA-IR at baseline (all P In conclusion, RBP4 is closely associated with glucose metabolism and insulin resistance in Chinese obese patients. The decreased RBP4 levels may partly account for the improved insulin sensitivity in obese subjects after LSG. Disclosure X. Wang: None. L. Li: None. C. Zhu: None. J. Gao: None. S. Qu: None.