Peripheral signalling involved in energy homeostasis control

Abstract

The alarming prevalence of obesity has led to a better understanding of the molecular mechanisms controlling energy homeostasis. Regulation of energy intake and expenditure is more complex than previously thought, being influenced by signals from many peripheral tissues. In this sense, a wide variety of peripheral signals derived from different organs contributes to the regulation of body weight and energy expenditure. Besides the well-known role of insulin and adipokines, such as leptin and adiponectin, in the regulation of energy homeostasis, signals from other tissues not previously thought to play a role in body weight regulation have emerged in recent years. The role of fibroblast growth factor 21 (FGF21), insulin-like growth factor 1 (IGF-I), and sex hormone-binding globulin (SHBG) produced by the liver in the regulation of body weight and insulin sensitivity has been recently described. Moreover, molecules expressed by skeletal muscle such as myostatin have also been involved in adipose tissue regulation. Better known is the involvement of ghrelin, cholecystokinin, glucagon-like peptide 1 (GLP-1) and PYY 3 -36 , produced by the gut, in energy homeostasis. Even the kidney, through the production of renin, appears to regulate body weight, with mice lacking this hormone exhibiting resistance to diet-induced obesity. In addition, the skeleton has recently emerged as an endocrine organ, with effects on body weight control and glucose homeostasis through the actions of bone-derived factors such as osteocalcin and osteopontin. The comprehension of these signals will help in a better understanding of the aetiopathology of obesity, contributing to the potential development of new therapeutic targets aimed at tackling excess body fat accumulation.

The role of protein in weight loss and maintenance

“…Clarification of the interactions between these drivers is just beginning to emerge. From 2000 to the present, much has been learned about the peripheral hormonal signals and central targets that influence energy intake (20)(21)(22). Dietary protein is an effective stimulus for the release or inhibition of many of these peptides (23)(24)(25).…”

Undernutrition, risk of malnutrition and obesity in gastroenterological patients: A multicenter study

“…Although the term malnutrition is commonly used in the sense of undernutrition, it encompasses both weight loss (undernutrition) and weight gain (overweight and obesity). The physiological basis of undernutrition and obesity is the deficit (undernutrition) or the excess (obesity) of calories that results in measurable adverse effects on clinical outcomes [1][2][3][4][5] . The equilibrium between the total energy requirements, nutrient intake and utilization is mediated by hormonal and cytokine stimuli that induce the activation of intracellular metabolic pathways.…”

Uroguanylin levels in intestine and plasma are regulated by nutritional status in a leptin-dependent manner

“…The gastrointestinal tract is an endocrine organ with various hormones secreted from endocrine cells and several neural pathways communicating information from the signals responsible for the regulation of energy homeostasis [1]. In the intestine, the large list of hormones include gastrin, cholecystokinin, oxyntomodulin, glucagon-like peptide one and peptide YY [2], all of which act as anorectic agents.…”

“…UGN is a 16 amino acid peptide secreted by intestinal epithelial cells as the prohormone prouroguanylin that requires enzymatic conversion into the active hormone [9]. UGN, as well as the other two members of this family, acts through a receptor named guanylyl cyclase 2C (GUCY2C) that is mainly expressed in intestinal epithelial cells [1,[10][11][12]. At intestinal level, UGN exerts a paracrine function and regulates physiological processes such as electrolyte and fluid balance, cellular metabolism and reorganization of intestinal crypt-villus axis [13].…”