Neurohormonal Changes in the Gut-Brain Axis and Underlying Neuroendocrine Mechanisms following Bariatric Surgery

Abstract

Obesity is a complex, multifactorial disease that is a major public health issue worldwide. Currently approved anti-obesity medications and lifestyle interventions lack the efficacy and durability needed to combat obesity, especially in individuals with more severe forms or coexisting metabolic disorders, such as poorly controlled type 2 diabetes. Bariatric surgery is considered an effective therapeutic modality with sustained weight loss and metabolic benefits. Numerous genetic and environmental factors have been associated with the pathogenesis of obesity, while cumulative evidence has highlighted the gut-brain axis as a complex bidirectional communication axis that plays a crucial role in energy homeostasis. This has led to increased research on the roles of neuroendocrine signaling pathways and various gastrointestinal peptides as key mediators of the beneficial effects following weight-loss surgery. The accumulate evidence suggests that the development of gut-peptide-based agents can mimic the effects of bariatric surgery and thus is a highly promising treatment strategy that could be explored in future research. This article aims to elucidate the potential underlying neuroendocrine mechanisms of the gut-brain axis and comprehensively review the observed changes of gut hormones associated with bariatric surgery. Moreover, the emerging role of post-bariatric gut microbiota modulation is briefly discussed.

Keywords: appetite; bariatric surgery; central nervous system; energy homeostasis; gut microbiota; gut peptides; gut–brain axis; neuropeptides.

Figure 1

Types of commonly performed bariatric surgery procedures. (Source: https://www.istockphoto.com/, accessed on 14 August 2021).

Figure 2

Neurohormonal circuits and neuronal signals derived from the hypothalamus and other centers regulating appetite and energy homeostasis, which may be affected by bariatric surgery. (Created in https://biorender.com/, accessed on 13 February 2022) AgRP: agouti-related peptide, ARC: arcuate nucleus, BDNF: brain-derived neurotrophic factor, CART: cocaine and amphetamine-regulated transcript, CCK: cholecystokinin, DMN: dorsomedial nucleus, GABA: γ-amino-butyric acid, GIP: gastric inhibitory polypeptide, GLP: glucagon-like peptide, LHA: lateral hypothalamic area, MCH: melanin-concentrating hormone, MC3R: melanocortin 3 receptor, MC4R: melanocortin-4 receptor, NPY: neuropeptide Y, OXM: oxyntomodulin, POMC: pro-opiomelanocortin, PYY: peptide YY, PVN: paraventricular nucleus, VMN: ventromedial nucleus.