Does gastric bypass surgery change body weight set point?

Abstract

The relatively stable body weight during adulthood is attributed to a homeostatic regulatory mechanism residing in the brain which uses feedback from the body to control energy intake and expenditure. This mechanism guarantees that if perturbed up or down by design, body weight will return to pre-perturbation levels, defined as the defended level or set point. The fact that weight re-gain is common after dieting suggests that obese subjects defend a higher level of body weight. Thus, the set point for body weight is flexible and likely determined by the complex interaction of genetic, epigenetic and environmental factors. Unlike dieting, bariatric surgery does a much better job in producing sustained suppression of food intake and body weight, and an intensive search for the underlying mechanisms has started. Although one explanation for this lasting effect of particularly Roux-en-Y gastric bypass surgery (RYGB) is simple physical restriction due to the invasive surgery, a more exciting explanation is that the surgery physiologically reprograms the body weight defense mechanism. In this non-systematic review, we present behavioral evidence from our own and other studies that defended body weight is lowered after RYGB and sleeve gastrectomy. After these surgeries, rodents return to their preferred lower body weight if over-or underfed for a period of time, and the ability to drastically increase food intake during the anabolic phase strongly argues against the physical restriction hypothesis. However, the underlying mechanisms remain obscure. Although the mechanism involves central leptin and melanocortin signaling pathways, other peripheral signals such as gut hormones and their neural effector pathways likely contribute. Future research using both targeted and non-targeted 'omics' techniques in both humans and rodents as well as modern, genetically targeted, neuronal manipulation techniques in rodents will be necessary.

Epigenetic contribution to obesity

“…It is well accepted that metabolic surgery is the most effective strategy to treat obesity and its associated comorbidities (Hao et al 2016 ; Schauer et al 2017 ). The review by Nicoletti et al summarizes genes which have been identified to be epigenetically altered after metabolic surgery.…”

Recent advances in understanding body weight homeostasis in humans

“…In addition, long-term adaptation and a stable body weight after weight loss following bariatric surgery has been proposed to reflect a permanent re-setting of the body weight set point, restoring “normal” leptin signaling (or its downstream signals) in the hypothalamus 60 , 61 . Accordingly, after bariatric surgery, the proposed re-programming of the body weight defense mechanisms at a lower body weight was not associated with increased hunger feelings or reduced EE 61 . By contrast, animal data suggest no increase in hypothalamic leptin sensitivity after weight loss due to bariatric surgery, questioning the idea of re-programming a set point 60 .…”

Turning the scale

“…Research shows that hormones controlling satiety, appetite and hunger are responsible for this 11 . Although the exact mechanisms are still being investigated, there is evidence that the set-point regulating body weight indeed is permanently set at a lower level 12,13 . After surgery, appetite is reduced and then followed by weight Interestingly, symptoms of diabetes may improve immediately after surgery, and many patients will have normal blood sugar levels and require less medication long before the weight loss has occurred 14 .…”