a1 Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain
a2 CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), ISCIII, Spain
a3 Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain
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 PYY3–36, 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.
(Received December 23 2011)
(Revised May 21 2012)
(Accepted May 22 2012)
Abbreviations: AgRP, Agouti-related peptide; AMPK, AMP-activated protein kinase; Ang, angiotensin; ANP, atrial natriuretic peptide; ASP, acylation-stimulating protein; BAT, brown adipose tissue; BNP, brain natriuretic peptide; CCK, cholecystokinin; CCK1R, cholecystokinin-1 receptor; cGMP, cyclic guanosine monophosphate; CNP, c-type natriuretic peptide; ER, oestrogen receptor; FGF, fibroblast growth factor; GIP, glucose-dependent insulinotropic polypeptide; GLP, glucagon-like peptide; GUCY, guanylyl cyclase; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; NPY, neuropeptide Y; POMC, pro-opiomelanocortin; PP, pancreatic polypeptide; PYY, peptide YY; SHBG, sex hormone-binding globulin; T2DM, type 2 diabetes mellitus; T3, triiodothyronine; THR, thyroid hormone receptor; vaspin, visceral adipose tissue-derived serpin