The role of gut hormones in the pathogenesis and management of obesity

Abstract

The growing obesity epidemic is driving the need for development of novel, effective therapeutic strategies for obesity and its complications. Increasing our understanding of the processes controlling body weight is therefore imperative. Gut hormones have emerged as essential regulators of energy homeostasis. Dysregulation of gut hormone physiology is increasingly implicated in obesity pathogenesis and the compensatory biological responses driving weight regain following energy restriction. Furthermore, gut hormones are among key mediators of the weight loss following Rouxen-Y gastric bypass and sleeve gastrectomy, the bariatric procedures which remain the most effective treatment for severe obesity. Therapeutic strategies targeting gut hormones and their receptors are driving a new pharmacotherapy era and constitute the most promising approach to addressing the obesity epidemic.

A state of the art review on the novel mediator asprosin in the metabolic syndrome

“…One target organ in the management of adiposity is the central nervous system: the response of hypothalamus to neurotransmitters released by the gastrointestinal tract plays a key role in energy homeostasis and appetite control. 14 …”

Intestinal Barrier Function and Immune Homeostasis Are Missing Links in Obesity and Type 2 Diabetes Development

“…The role of the intestine in metabolic homeostasis has been mainly ascribed to enteroendocrine cells, that act as sensors for nutritional signals and produce and secrete key hormones, such as glucose-dependent insulinotropic polypeptide (GIP), glucacon-like peptide 1 (GLP-1) and peptide YY, into the circulation ( 46 , 47 ). Of these hormones, GIP and GLP-1, commonly referred to as incretins, modulate postprandial glucose concentrations by inducing a rapid and strong insulinotropic effect after meal ingestion, which is blunted in patients with T2D ( 48 ) and has been widely explored as pharmaceutical target for T2D.…”

Psychobiology of Appetite and Food Reward in Adults with Type 1 and Type 2 Diabetes: Is there a Role for Exercise?

“…Vagal afferent sensitivity to CCK is enhanced by the release of gastric leptin upon meal consumption (an effect separate to the tonic influence of adipose-derived leptin) [5]. These 'satiety' hormones act synergistically with their co-secretion enhancing their individual anorexigenic properties [6]. The orexigenic hormone ghrelin, secreted by gastric cells in the absence of nutrients in the gastrointestinal tract, inhibits vagal afferent sensitivity to gastric distention and CCK to promote hunger [2].…”

“…Ghrelin, insulin, and leptin are also able to cross the blood-brain barrier, acting directly on the brain stem to mediate feeding behaviour [7]. It is worth noting however that these gastrointestinal hormones have a range of functions associated with gastrointestinal motility and nutrient digestion and absorption [6],…”