Please use this identifier to cite or link to this item:
|Title:||Deletion of Tumor necrosis factor-α receptor 1 (TNFR1) protects against diet-induced obesity by means of increased thermogenesis|
Roman, Erika A.
Arruda, Ana P.
Denis, Raphael G.
Moraes, Juliana C.
Bonfleur, Maria L.
Degasperi, Giovanna R.
Picardi, Paty K.
Boschero, Antonio C.
Velloso, Licio A.
|Abstract:||In diet-induced obesity, hypothalamic and systemic inflammatory factors trigger intracellular mechanisms that lead to resistance to the main adipostatic hormones, leptin and insulin. Tumor necrosis factor-α (TNF-α) is one of the main inflammatory factors produced during this process and its mechanistic role as an inducer of leptin and insulin resistance has been widely investigated. Most of TNF-α inflammatory signals are delivered by TNF receptor 1 (R1); however, the role played by this receptor in the context of obesity-associated inflammation is not completely known. Here, we show that TNFR1 knock-out (TNFR1 KO) mice are protected from diet-induced obesity due to increased thermogenesis. Under standard rodent chow or a high-fat diet, TNFR1 KO gain significantly less body mass despite increased caloric intake. Visceral adiposity and mean adipocyte diameter are reduced and blood concentrations of insulin and leptin are lower. Protection from hypothalamic leptin resistance is evidenced by increased leptin-induced suppression of food intake and preserved activation of leptin signal transduction through JAK2, STAT3, and FOXO1. Under the high-fat diet, TNFR1 KO mice present a significantly increased expression of the thermogenesis-related neurotransmitter, TRH. Further evidence of increased thermogenesis includes increased O2 consumption in respirometry measurements, increased expressions of UCP1 and UCP3 in brown adipose tissue and skeletal muscle, respectively, and increased O2 consumption by isolated skeletal muscle fiber mitochondria. This demonstrates that TNF-α signaling through TNFR1 is an important mechanism involved in obesity-associated defective thermogenesis|
|Subject:||Fator de necrose tumoral alfa|
|Editor:||American Society for Biochemistry and Molecular Biology|
|Appears in Collections:||FCM - Artigos e Outros Documentos|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.