Gut Factors Mediating the Physiological Impact of Bariatric Surgery

Abstract

Despite decades of obesity research and various public health initiatives, obesity remains a major public health concern. Our most drastic but most effective treatment of obesity is bariatric surgery with weight loss and improvements in co-morbidities, including resolution of type 2 diabetes (T2D). However, the mechanisms by which surgery elicits metabolic benefits are still not well understood. One proposed mechanism is through signals generated by the intestine (nutrients, neuronal, and/or endocrine) that communicate nutrient status to the brain. In this review, we discuss the contributions of gut-brain communication to the physiological regulation of body weight and its impact on the success of bariatric surgery. Advancing our understanding of the mechanisms that drive bariatric surgery-induced metabolic benefits will ultimately lead to the identification of novel, less invasive strategies to treat obesity.

Keywords: Bariatric surgery; Gut hormones; Obesity.

Fig. 1

Anatomical and metabolic changes induced by vertical sleeve gastrectomy or Roux-en-Y gastric bypass. A) VSG is a procedure where 80% of the stomach along the greater curvature is removed. RYGB creates a gastric pouch and the intestine is rearranged such that ingested food bypasses 95% of the stomach and the upper intestinal tract. B) While the anatomy of RYGB and VSG surgeries differ, the two share similarities such as increases in sustained weight loss and rapid nutrient entry as well as the resolution of Type 2 Diabetes and some mild differences in gut peptide responses. Created with BioRender.com

Fig. 2

Changes in food intake and body weight over time in rodent models of bariatric surgery. Food intake after bariatric surgery in rodents is reduced during the first two–three weeks post-operatively, and then returns to, but never exceeds, the level of food intake seen in the sham animals [10, 11]. If an animal is food restricted (FR) for a period of time and body weight is lost, once returned to ad lib feeding, the animal will ingest more food than unrestricted animals until body weight returns to what it would have been had the animal never been restricted, something that does not occur with VSG [10]. Overall, this suggests that there are two phases to bariatric surgery, the initial weight loss phase with reduced food intake, and a second phase where hyperphagia is prevented and the weight loss is sustained

Fig. 3

Summary of intestinal signals and cues that are altered after bariatric surgery. 1) After VSG and RYGB there are changes in the flow of nutrients, gut-generated peptides, and neuronal activation. 2) Increases in nutrient flow along with alterations in nutrient handling (i.e., increased glucose rate of appearance) can lead to the increased secretion of gut signals such as hormones and bile acids. Specific regions of the CNS (NTS and AP) are also activated after a meal. This increased activation may be due to direct neural innervation, the altered nutrient flow 3) or increases in gut-generated signals, such as 4) gut peptides, FGF19/15, bile acids, and/or the microbiome. Created with BioRender.com