Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms
Sean Manning, … , Andrea Pucci, Rachel L. Batterham
Sean Manning, … , Andrea Pucci, Rachel L. Batterham
Published March 2, 2015
Citation Information: J Clin Invest. 2015;125(3):939-948. https://doi.org/10.1172/JCI76305.
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Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

Abstract

Bariatric surgery is the most effective treatment for severe obesity, producing marked sustained weight loss with associated reduced morbidity and mortality. Roux-en-Y gastric bypass surgery (RYGBP), the most commonly performed procedure, was initially viewed as a hybrid restrictive-malabsorptive procedure. However, over the last decade, it has become apparent that alternative physiologic mechanisms underlie its beneficial effects. RYGBP-induced altered feeding behavior, including reduced appetite and changes in taste/food preferences, is now recognized as a key driver of the sustained postoperative weight loss. The brain ultimately determines feeding behavior, and here we review the mechanisms by which RYGBP may affect central appetite-regulating pathways.

Authors

Sean Manning, Andrea Pucci, Rachel L. Batterham

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Figure 1

Schematic diagram illustrating the mechanisms involved in regulating feeding behavior.

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Schematic diagram illustrating the mechanisms involved in regulating fee...
Nutrient entry into the GI tract causes stomach and intestine distension, secretion of pancreatic enzymes and bile acids, altered enteric and vagal nerve signaling, 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 (nutrient, hormonal, and neural) and adipokines (e.g., leptin, IL-6, TNF-α, 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, which influence the thyroid and adrenal hormonal axes, and in the LHA. Altered brainstem and hypothalamic activation influence brain reward and higher cognitive brain regions and together lead to altered feeding behavior. Abbreviations: ACTH, adrenocorticotrophic hormone; AgRP, agouti-related peptide; ARC, arcuate nucleus; AVP, vasopressin; CART cocaine and amphetamine-regulated transcript; CRH, corticotropin-releasing hormone; ENS, enteric nervous system; FGF-19, fibroblast growth factor 19; LHA, lateral hypothalamic area; MSH, melanocortin-stimulating hormone; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; NT, neurotensin; OREX, orexin; OT, oxytocin; PVN, paraventricular nucleus; TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone; PNS, peripheral nervous system; SNS, sympathetic nervous system; ACTH, adrenocorticotrophic hormone, ENS, enteric nervous system.