Adiposity signals, genetic and body weight regulation in humans

• Published in: Diabetes & metabolism 2004-06, Vol.30 (3), p.215-227
• Main Authors: Cancello, R, Tounian, A, Poitou, Ch, Clément, K
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipose Tissue - anatomy & histology; Adipose Tissue - physiology; Adiposity signal; Animals; Biological and medical sciences; Body Weight - genetics; Cytokines - physiology; Homeostasis; Humans; Inflammation; Inflammation - physiopathology; Insulin; Insulin - physiology; Insuline; Leptin; Leptin - physiology; Leptine; Medical sciences; Metabolic diseases; Metabolic signals; Obesity; Obesity - genetics; Obésité; Signal d'adiposité; Signal Transduction; Signaux métaboliques; Tissu adipeux blanc; White adipose tissue
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/S1262-3636(07)70112-X

Numerous signals convey information about body fat status from the periphery to the brain areas that control energy homeostasis so that, throughout life, body weight remains nearly stable. These signals mainly originate, either from the adipose tissue, like leptin and to a lesser extent interleukin 6, or from the pancreas, like insulin and amylin. These factors circulate in proportion to body fat mass and they are referred to as “adiposity signals”. It is well established, at least for leptin and insulin, that they enter the brain from the plasma where they induce/repress a network of important neuropeptide regulators of energy intake and expenditure. Beside these endocrine signals, a growing amount of literature show data relative to adipocyte-derived molecules, most of them belonging to the cytokine family, like IL6, TNFα, IL8, IL10 whose secretion also correlates with body fat mass and that may locally regulate fat mass expansion. Others, like Adiponectin, are negatively correlated with body fat mass. These “adiposity molecules” have already been involved in insulin resistance associated with obesity and inflammatory process. They may participate to a complex inter organ dialogue. In this review, we will synthesize data relative to the role played by insulin, leptin and amylin, either alone or through a cross talk, in “energy level sensing” at the brain level. Furthermore, we will develop how “adiposity molecules” through their paracrin and/or autocrin action may contribute to maintain fat mass expansion, therefore representing new adiposity molecules per se. Lastly, since any distortion in the metabolic circuitry of energy homeostasis is susceptible to lead to a pathological status like obesity, the impact of known genetic polymorphisms in genes encoding the adiposity signals will be discussed. Signaux d'adiposité, génétique et régulation du poids corporel chez l'homme De nombreux signaux transmettent au cerveau des informations sur le statut des réserves d'énergie contribuant ainsi au contrôle de la balance énergétique et au maintien d'un poids relativement stable. Ces signaux sont produits par le tissu adipeux comme la leptine et l'interleukine 6 ou par le pancréas, comme l'insuline et l'amyline. Ces facteurs circulent en proportion de la masse graisseuse et sont appelés classiquement des signaux d'adiposité. Il est bien établi, au moins pour la leptine et l'insuline, que ces molécules sont transférées de la circulation vers le cerveau où elles indui