The Role of GLP-1 in the Metabolic Success of Bariatric Surgery

Abstract

Two of the most popular bariatric procedures, vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB), are commonly considered metabolic surgeries because they are thought to affect metabolism in a weight loss-independent manner. In support of this classification, improvements in glucose homeostasis, insulin sensitivity, and even discontinuation of type 2 diabetes mellitus (T2DM) medication can occur before substantial postoperative weight loss. The mechanisms that underlie this effect are unknown. However, one of the common findings after VSG and RYGB in both animal models and humans is the sharp postprandial rise in several gut peptides, including the incretin and satiety peptide glucagonlike peptide-1 (GLP-1). The increase in endogenous GLP-1 signaling has been considered a primary pathway leading to postsurgical weight loss and improvements in glucose metabolism. However, the degree to which GLP-1 and other gut peptides are responsible for the metabolic successes after bariatric surgery is continually debated. In this review we discuss the mechanisms underlying the increase in GLP-1 and its potential role in the metabolic improvements after bariatric surgery, including remission of T2DM. Understanding the role of changes in gut peptides, or lack thereof, will be crucial in understanding the critical factors necessary for the metabolic success of bariatric surgery.

Figure 1.

Summary of peptide responses after VSG and RYGB in human and animal models. Horizontal arrow indicates mixed results in the literature. N/A, no change with surgery or not well studied; OXY, oxyntomodulin.

Figure 2.

Proposed postprandial GLP-1 action after bariatric surgery. GLP-1 has a wide array of physiological effects. Some effects that are thought to play a role in responses to bariatric surgery include reductions in (1) food intake and, consequently, weight loss, (2) decreased fasting insulin levels, (3) increased incretin effects (greater GLP-1 leads to greater postprandial insulin), and (4) reduced hepatic glucose production. Both clinical and preclinical work support the role of GLP-1 in increasing postprandial insulin levels. However, it is less clear whether GLP-1 directly affects weight loss and T2DM remission associated with surgery.

Figure 3.

Similarities and differences in anatomy and outcomes in response to RYGB and VSG. After RYGB (left), a small gastric pouch is made and is anastomosed to the jejunum, bypassing the majority of the stomach and upper intestinal tract. After VSG (right), 80% of the stomach along the greater curvature is removed without intestinal rearrangement to preserve the flow of nutrients through the proximal GI tract. Both surgeries (middle) result in improvements in reduced hepatic glucose production (HGP), increased postprandial insulin secretion, increase nutrient entry rate into the intestine, and increased nutrient-induced gut peptide release, including GLP-1 secretion. Both surgeries also cause weight loss and, in many cases, remission of T2DM.