PMID- 31079286 OWN - NLM STAT- MEDLINE DCOM- 20200520 LR - 20200520 IS - 1708-0428 (Electronic) IS - 0960-8923 (Linking) VI - 29 IP - 9 DP - 2019 Sep TI - Roux-en-Y Gastric Bypass Improves Metabolic Conditions in Association with Increased Serum Bile Acids Level and Hepatic Farnesoid X Receptor Expression in a T2DM Rat Model. PG - 2912-2922 LID - 10.1007/s11695-019-03918-0 [doi] AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and liver morphological adaption, as well as the changes in bile acids signaling and expression of its target regulatory factors involved in gluconeogenesis, lipogenesis, and fatty acid beta oxidation. METHODS: Twenty adult male T2DM rats induced by high-fat diet and a low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, serum lipid profiles, and bile acids level were assessed to evaluate metabolic changes. Liver sections were stained with hematoxylin-eosin (H&E) and oil red O to assess lipid accumulation. The mRNA and protein expression levels of farnesoid X receptor (FXR), small heterodimer partner (SHP), key regulatory factors of gluconeogenesis, lipogenesis, and fatty acid beta oxidation (phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-alpha (PPAR-alpha)) were determined through RT-PCR and Western blotting, respectively. RESULTS: RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum TG, FFAs, and increased bile acids levels. The lipid droplets in the liver were significantly decreased after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK, G6Pase, and SREBP-1c and upregulated expression of FXR, SHP, and PPAR-alpha in the liver. CONCLUSIONS: RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The liver exhibited a marked improvement in lipid accumulation after RYGB. The bile acids level, FXR, and its target transcriptional factor SHP expression were elevated. Meanwhile, our study demonstrated that the increased bile acids-FXR signaling, followed by the reduced hepatic gluconeogenesis, lipogenesis, and increased fatty acid beta oxidation may contribute to improved metabolic conditions after RYGB. FAU - Yan, Yong AU - Yan Y AUID- ORCID: 0000-0002-8128-4353 AD - Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, 510220, China. FAU - Sha, Yanhua AU - Sha Y AD - Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China. FAU - Huang, Xianzhang AU - Huang X AD - Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China. FAU - Yuan, Wei AU - Yuan W AD - Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, 510220, China. FAU - Wu, Fan AU - Wu F AD - Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, 510220, China. FAU - Hong, Jinsong AU - Hong J AD - Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, 510220, China. FAU - Fang, Shaomei AU - Fang S AD - Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, 510220, China. FAU - Huang, Bo AU - Huang B AD - Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, 510220, China. FAU - Hu, Cheng AU - Hu C AD - Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. FAU - Wang, Bailin AU - Wang B AD - Department of General Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, 510220, China. wangbailin888@sina.com. FAU - Zhang, Xueli AU - Zhang X AD - Department of General Surgery, Central Hospital of Fengxian District, Southern Medical University, No.6600, Nan Feng Road, Shanghai, 201499, China. lejing1996@aliyun.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Obes Surg JT - Obesity surgery JID - 9106714 RN - 0 (Bile Acids and Salts) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (nuclear receptor subfamily 0, group B, member 2) RN - 0C5V0MRU6P (farnesoid X-activated receptor) RN - 5W494URQ81 (Streptozocin) RN - EC 3.1.3.9 (Glucose-6-Phosphatase) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Bile Acids and Salts/*metabolism MH - Diabetes Mellitus, Type 2/*metabolism/*surgery MH - Diet, High-Fat MH - *Gastric Bypass MH - Gluconeogenesis MH - Glucose/metabolism MH - Glucose-6-Phosphatase/metabolism MH - Homeostasis MH - Insulin Resistance MH - Lipid Metabolism MH - Lipogenesis MH - Liver/metabolism MH - Male MH - Obesity, Morbid/metabolism/surgery MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Cytoplasmic and Nuclear/*metabolism MH - Streptozocin MH - Weight Loss OTO - NOTNLM OT - Bariatric surgery OT - Bile acids OT - Farnesoid X receptor OT - Gluconeogenesis OT - Glucose homeostasis OT - High-fat diet OT - Lipid profiles OT - Lipogenesis OT - Roux-en-Y gastric bypass OT - Small heterodimer partner OT - Streptozotocin OT - Type 2 diabetes mellitus EDAT- 2019/05/13 06:00 MHDA- 2020/05/21 06:00 CRDT- 2019/05/13 06:00 PHST- 2019/05/13 06:00 [pubmed] PHST- 2020/05/21 06:00 [medline] PHST- 2019/05/13 06:00 [entrez] AID - 10.1007/s11695-019-03918-0 [pii] AID - 10.1007/s11695-019-03918-0 [doi] PST - ppublish SO - Obes Surg. 2019 Sep;29(9):2912-2922. doi: 10.1007/s11695-019-03918-0.