Recent advances in the mechanisms underlying the beneficial effects of bariatric and metabolic surgery

Abstract

Bariatric and metabolic surgery (BMS) is the most effective treatment for obesity, type 2 diabetes and co-morbidities, including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The beneficial effects of BMS are beyond the primary goal of gastric restriction and nutrients malabsorption. Roux-en-Y gastric bypass and vertical sleeve gastrectomy are the 2 most commonly performed procedures of BMS. Both surgeries lead to physiologic changes in gastrointestinal tract; subsequently alter bile acids pool and composition, gut microbial activities, gut hormones, and circulating exosomes; and ultimately contribute to the improved glycemic control, insulin sensitivity, lipid metabolism, energy expenditure, and weight loss. The mechanisms underlying the benefits of BMS likely involve the bile acid-signaling pathway mediated mainly by nuclear farnesoid X receptor and the membrane Takeda G protein-coupled receptor, bile acids-gut microbiota interaction, and exosomes. In this review, we focus on recent advances in potential mechanisms and aim to learn novel insights into the molecular mechanisms underlying metabolic disorders.

Keywords: Bariatric and metabolic surgery; Bile acids; FXR; NAFLD; T2D; TGR5.

Figure. 1.. Vertical sleeve gastrectomy (VSG).

Schematic diagram of VSG. VSG creates a tube-like stomach with the majority (approximately 70–80%) of stomach is removed along the greater curvature. The dotted line denote where the excision is made (in between).

Figure. 2.. Roux-en-Y Gastric Bypass (RYGB).

Schematic diagram of RYGB. The stomach is divided into a small gastric pouch and a distal stomach along the dotted lines. The jejunum is transected and the distal part is connected to the gastric pouch through a gastro-jejunostomy, which creates a Roux limb or alimentary limb, as indicated. The continuity of the gastrointestinal tract is re-established by connecting biliopancreatic limb to the jejunum through a jejunojejunostomy. The small intestine distal to the jejuno-jejunostomy is called common limb. RYGB leads ingested food to bypass the distal stomach, duodenum and proximal jejunum, and rapidly go through the small gastric pouch and flow into the jejunum. Therefore, nutrients are present in the Roux limb without bile, whereas bile and pancreatic secretions are present in the biliopancreatic limb, but no nutrients. Nutrients are mixed with bile and pancreatic secretions in the common limb.