Sir David Cuthbertson Medal Lecture Bariatric surgery as a model to study appetite control

Abstract

The obesity epidemic and its associated morbidity and mortality have led to major research efforts to identify mechanisms that regulate appetite. Gut hormones have recently been found to be an important element in appetite regulation as a result of the signals from the periphery to the brain. Candidate hormones include ghrelin, peptide YY, glucagon-like peptide-1 and gastric inhibitory polypeptide, all of which are currently being investigated as potential obesity treatments. Bariatric surgery is currently the most effective therapy for substantial and sustained weight loss. Understanding how levels of gut hormones are modulated by such procedures has greatly contributed to the comprehension of the underlying mechanisms of appetite and obesity. The present paper is a review of how appetite and levels of gastrointestinal hormones are altered after bariatric surgery. Basic principles of common bariatric procedures and potential mechanisms for appetite regulation by gut hormones are also addressed.

The effects of weight loss strategies on gastric emptying and appetite control

“…It is critical to determine whether alterations in GI function occur in response to weight loss or the treatment strategy per se and to distinguish between changes in fasting and postprandial and exogenous and endogenous levels of peptides. While bariatric surgery may be used as a model to understand physiological weight loss (39), the mechanisms influencing the emptying rate after surgery may be different to those that influence gastric emptying after other interventions. This review has considered the effects of different strategies on gut peptides as currently measured in the systemic circulation.…”

“…Reduced ghrelin levels after RYGB have also been implicated (24). However, increased, decreased and unchanged fasting ghrelin levels after surgery have been reported (39). Instead, the majority of studies suggest that the efficacy of RYGB in reducing appetite and promoting weight loss may relate predominantly to distal small intestinal effects (95).…”

“…Fasting levels of ghrelin increase in response to diet‐ and exercise‐induced energy deficits (30,36–38). Following bariatric surgery, changes in ghrelin levels are equivocal (39). However, in one study increased fasting ghrelin levels were observed in individuals who were in negative energy balance and not in those in energy balance (21), suggesting the energy balance state could explain some of the ambiguity in findings.…”

The physiology underlying Roux-en-Y gastric bypass: a status report

“…It is surprising, however, that qualitatively, the majority of effects that we describe here seem to be very robust and can be observed irrespective of slight differences in the surgical approach, the laboratory where the studies have been performed, the feeding history of the animals before or after surgery, the duration of presurgical obesity, the animals' weight and adiposity level at the time of surgery, the duration between surgery and metabolic testing, and other factors that may potentially affect the outcome of the study. Hence, because of space limitations, exact details of the experimental designs of the studies cited in this review will be given only when needed.Current research often focuses on altered concentrations of gut hormones like glucagon-like peptide-1 (GLP-1) or peptide YY (PYY) and metabolites (e.g., bile acids) that are known to affect eating and to modulate nutrient metabolism (6,16,17,29,41,66,67,70,73,114,133). It needs to be pointed out, however, that association and causality must not be confounded because measurable changes in circulating parameters after bariatric surgery do not necessarily play a causal role for the observed effects of bariatric surgery; hence, it is not yet clear whether these changes alone or in combination are necessary or sufficient for reduced eating or body weight.…”

“…Current research often focuses on altered concentrations of gut hormones like glucagon-like peptide-1 (GLP-1) or peptide YY (PYY) and metabolites (e.g., bile acids) that are known to affect eating and to modulate nutrient metabolism (6,16,17,29,41,66,67,70,73,114,133). It needs to be pointed out, however, that association and causality must not be confounded because measurable changes in circulating parameters after bariatric surgery do not necessarily play a causal role for the observed effects of bariatric surgery; hence, it is not yet clear whether these changes alone or in combination are necessary or sufficient for reduced eating or body weight.…”