Roux-en-Y Gastric Bypass in Obese Diabetic Rats Promotes Autophagy to Improve Lipid Metabolism through mTOR/p70S6K Signaling Pathway

Abstract

Purpose. To investigate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics and find new therapeutic basis on obese type 2 diabetes mellitus (T2DM) patients. Materials and Methods. Thirty-two rats were divided into nondiabetic group, diabetic group, sham group, and RYGB group. The Dual-energy X-ray absorptiometry (DEXA) was used to detect short-term curriculum vitae for rat body component and fat and lean mass. Hepatic lipid content and triglyceride levels were detected by Oil Red O staining. Western blotting was used to examine autophagy and mammalian target of rapamycin/P70S6 kinase (mTOR/p70S6K) pathway-related proteins. The carbon dioxide production from the oxidation of [14C] oleate was measured. Plasma glucose was measured by glucose oxidase assay. The insulin and C-peptide were detected. Triacylglyceride (TG) and free fat acid (FFA) in plasma were determined by enzymatic colorimetric assays. Results. RYGB improved metabolic parameters and enhanced plasma GLP-1 level, ameliorated the lipopexia, and increased insulin sensitivity in the liver; RYGB promoted the hepatic autophagy and inhibited the mTOR/p70S6K signaling pathway. GLP-1 reduced fat load and increased fatty acid β-oxidation by activated autophagy to regulate the hepatic lipid pathway through mTOR/p70S6K signaling pathway. Conclusions. RYGB may reduce liver lipid toxicity and improve insulin sensitivity through activating the hepatic fat hydrolysis pathway and inhibiting the liver fat synthesis pathway. However, the transport pathway of liver fat does not play a key role.

Autophagy in Hepatic Steatosis: A Structured Review

“…Accordingly, high-fat fed rats submitted to sleeve gastrectomy showed significant TG reduction, and lower markers of ER stress and UPR activation, accompanied by increased β-oxidation, AMPK and autophagic activation (Ezquerro et al, 2016(Ezquerro et al, , 2020. Similar changes were found using roux-en-Y gastric bypass interventions (He et al, 2015;Ma et al, 2020). ER stress and UPR activation are common findings in the steatotic liver of rodents and humans, and many targets have been suggested as possible points of intervention for NAFLD treatment (Lebeaupin et al, 2018).…”

“…In fact, liver-specific AMPK activation was shown to counteract steatosis development during obesity by different mechanisms, including autophagy activation . Bariatric surgery in rodents, for instance, improves steatosis while increasing AMPK and decreasing mTORC1 activation (Ezquerro et al, 2016;Ma et al, 2020). Moreover, increased cytosolic acetyl-CoA derived from peroxisomal β-oxidation present in the liver of HFD fed animals was shown to promote mTOR localization at the lysosome surface, increasing ULK1 phosphorylation by mTORC1 and inhibiting autophagy (He et al, 2020).…”

Roux-en-Y Gastric Bypass Modulates AMPK, Autophagy and Inflammatory Response in Leukocytes of Obese Patients

“…However, few studies have evaluated the possible interaction between autophagy and weight loss in obese models. Previous research has shown that the downregulation of hepatic autophagy in high-fat diet-induced obesity promotes ER stress and IR [ 51 , 52 ], whereas RYGB is reported to improve hepatic lipid metabolism through an increase in the LC3-II/LC3-I ratio and the down-regulation of mTOR [ 53 ]. In the case of 3T3-L1 preadipocytes, the recent report published by Zhang et al [ 54 ] points to autophagy as the molecular effector that restores lipid accumulation in adipocytes through activation of autophagy and chaperone-mediated autophagy.…”

The Metabolite β-Hydroxybutyrate of Lactobacillus Plantarum YZX21 Improves Type 2 Diabetes By Promoting Intestinal Secretion of GLP-1

“…Studies found that high levels of FFA inhibit GLP-1 [30]. Inhibiting FFA levels can increase GLP-1 secretion, thereby improving T2DM [7,31]. Studies have shown that BHB signi cantly improved tissue damage, metabolic disorders and protein metabolism [32].…”