Mechanisms underlying the weight loss effects of RYGB and SG: similar, yet different

Abstract

The worldwide obesity epidemic continues unabated, adversely impacting upon global health and economies. People with severe obesity suffer the greatest adverse health consequences with reduced life expectancy. Currently, bariatric surgery is the most effective treatment for people with severe obesity, resulting in marked sustained weight loss, improved obesity-associated comorbidities and reduced mortality. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), the most common bariatric procedures undertaken globally, engender weight loss and metabolic improvements by mechanisms other than restriction and malabsorption. It is now clear that a plethora of gastrointestinal (GI) tract-derived signals plays a critical role in energy and glucose regulation. SG and RYGB, which alter GI anatomy and nutrient flow, impact upon these GI signals ultimately leading to weight loss and metabolic improvements. However, whilst highly effective overall, at individual level, post-operative outcomes are highly variable, with a proportion of patients experiencing poor long-term weight loss outcome and gaining little health benefit. RYGB and SG are markedly different anatomically and thus differentially impact upon GI signalling and bodyweight regulation. Here, we review the mechanisms proposed to cause weight loss following RYGB and SG. We highlight similarities and differences between these two procedures with a focus on gut hormones, bile acids and gut microbiota. A greater understanding of these procedure-related mechanisms will allow surgical procedure choice to be tailored to the individual to maximise post-surgery health outcomes and will facilitate the discovery of non-surgical treatments for people with obesity.

Keywords: Bile acids; Gut hormones; Gut microbiota; Roux-en-Y gastric bypass; Sleeve gastrectomy; Type 2 diabetes.

Fig. 1

Schematic diagram illustrating the normal upper GI anatomy (a) and the two most commonly performed bariatric surgical procedures in the world with relative percentages. The metabolic procedures: b RYGB and c SG (surgical technique described in details in the main text). RYGB were the 39.6% and SG were the 45.9% of the total procedures performed in 2014 [12]. RYGB Roux-en-Y gastric bypass, SG Sleeve gastrectomy

Fig. 2

Schematic diagram illustrating the mechanisms involved in regulating feeding behaviour. Nutrient entry into the GI tract causes stomach and intestine distension, secretion of pancreatic enzymes and BA, altered enteric and vagal nerve signalling and exposure of gut enteroendocrine cells to nutrients with altered circulating gut hormone levels (e.g. decrease in orexigenic hormone ghrelin and increase in anorectic hormones PYY3-36 and GLP-1). Gut-derived signals (nutrients, hormones, and neural) and adipokines (e.g. leptin, IL-6, TNF-alpha and adiponectin) act directly and indirectly upon brainstem and hypothalamic arcuate nuclei (first order neurons: orexigenic NPY/AgRP and anorexigenic POMC/CART). ARC neurons interact with second order neurons in the PVN, and to the LHA. All those mechanisms are involved in the regulation of homeostatic hunger. Social factors, emotion, reward, pleasure, increased food availability and sensory cues can influence brain reward and higher cognitive brain regions leading to altered feeding behaviour (hedonic hunger). Taste and olfactory signals can also influence energy intake acting on both homeostatic and brain reward systems. Insulin leptin, GLP-1, PYY and ghrelin are present in saliva with cognate receptors on taste buds and olfactory neurons. AgRP agouti-related peptide, ARC arcuate nucleus, CART cocaine and amphetamine-regulated transcript, FGF-19 fibroblast growth factor-19, GLP-1 glucagon-like peptide 1, IL-6 interleukin-6, LHA lateral hypothalamic area, NPY neuropeptide Y, PNS peripheral nervous system, PVN paraventricular nucleus, PYY3-36 peptide tyrosine–tyrosine 3-36, POMC pro-opiomelanocortin, SNS sympathetic nervous system

Fig. 3

Schematic diagram illustrating the different biological changes induced by weight loss obtained through dieting (upper part) compared to bariatric/metabolic surgery (lower part). Powerful compensatory biological changes contribute to the high rate of weight recidivism observed following lifestyle intervention weight management. Many homeostatic mechanisms act to defend higher body weight, and these includes hormonal alterations and a decreased energy expenditure leading to increased hunger and energy consumption. In contrast, bariatric surgery leads to a favourable biology that includes increased satiety hormones, reduced ghrelin, enhanced BA secretion and a “lean” microbiota. Together these mechanisms lead to reduced hunger and a shift towards healthier food options with a resetting of body weight “set point” to a lower level facilitating meaningful and sustained weight loss. GLP-1 glucagon-like peptide 1, PYY3-36 peptide tyrosine–tyrosine 3-36. *Suggestion that leptin sensitivity may improve References for this figure [5, 60, 96]

Fig. 4

Schematic diagram illustrating RYGB and SG and the mechanisms leading to weight loss and resolution of comorbidities. For every mechanism the effect of the procedure is represented with a “↑” when stimulating or “↓” when suppressing. A “+” means that the proposed mechanism is present only after surgery when compared to the pre-operative period. When the effect is stronger for one of the two procedures there is a double arrow compared with a single one. When the effect is missing for one procedure it means that the mechanism is procedure specific. RYGB Roux-en-Y gastric bypass, SG Sleeve gastrectomy, GLP-1 glucagon-like peptide 1, PYY3-36 peptide tyrosine–tyrosine 3-36, GIP gastric inhibitory polypeptide, FGF-19 fibroblast growth factor-19, CCK cholecystokinin