The Metabolic Rearrangements of Bariatric Surgery: Focus on Orexin-A and the Adiponectin System

Abstract

The accumulation of adipose tissue represents one of the characteristics of obesity, increasing the risk of developing correlated obesity diseases such as cardiovascular disease, type 2 diabetes, cancer, and immune diseases. Visceral adipose tissue accumulation leads to chronic low inflammation inducing an imbalanced adipokine secretion. Among these adipokines, Adiponectin is an important metabolic and inflammatory mediator. It is also known that adipose tissue is influenced by Orexin-A levels, a neuropeptide produced in the lateral hypothalamus. Adiponectin and Orexin-A are strongly decreased in obesity and are associated with metabolic and inflammatory pathways. The aim of this review was to investigate the involvement of the autonomic nervous system focusing on Adiponectin and Orexin-A after bariatric surgery. After bariatric surgery, Adiponectin and Orexin-A levels are strongly increased independently of weight loss showing that hormone increases are also attributable to a rearrangement of metabolic and inflammatory mediators. The restriction of food intake and malabsorption are not sufficient to clarify the clinical effects of bariatric surgery suggesting the involvement of neuro-hormonal feedback loops and also of mediators such as Adiponectin and Orexin-A.

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

“…Studies have shown that the presence of LHA lesions reduces body weight and adipose tissue in rats, indicating that it may play a critical role in regulating appetite [ 56 , 57 ]. Orexin A and B are produced from orexin neurons in the LHA and are important neuropeptides that are involved in the regulation of energy balance [ 58 ]. Orexin A acts through its receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R), to increase food intake as well as induce behavioral changes related to food reward [ 58 , 59 ].…”

“…Orexin A and B are produced from orexin neurons in the LHA and are important neuropeptides that are involved in the regulation of energy balance [ 58 ]. Orexin A acts through its receptors, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R), to increase food intake as well as induce behavioral changes related to food reward [ 58 , 59 ]. Similar orexigenic activity is displayed by MCH, as demonstrated by experimental studies which showed that MCH gene overexpression resulted in increased food intake and obesity in mice [ 60 ].…”

“…Additionally, neuropeptide alterations have been observed in the LHA after BS. Studies have shown that orexin levels are affected by bariatric surgery [ 58 ]. Gupta et al noted a decrease in orexin levels in some patients, whereas others had an increase in this neuropeptide after BPD-DS in the early post-operative period and before any weight loss [ 98 ].…”

“…On the contrary, a study by Cigdem et al observed significant weight loss and decreased orexin levels after laparoscopic GB [ 99 ]. The exact mechanism by which BS affects the orexin levels and how this contributes to the effects seen after BS is still unclear and most likely involves complex neuro-hormonal feedback loops [ 58 ]. Barkholt et al explored the effect of RYGB on MCH in the LHA and ARC in rats [ 87 ].…”

Novel Insight into the Mechanism of Metabolic Surgery Causing the Diversity in Glycemic Status in Type 2 Diabetes

“…Currently, two independent studies have shown that in diet-induced obese mice with T2D, RYGB and VSG can down-regulate ex-pression of pro-inflammatory genes, normalize hypothalamic inflammation, and improve glucose tolerance [88,89]. Surgical intervention has been reported to increase vagal tone in rodents [90,91]. The efferent vagus nerve-based cholinergic anti-inflammatory pathway was identified to control peripheral inflammation [92].…”