Paradoxical role of tumor necrosis factor on metabolic dysfunction and adipose tissue expansion in mice

Tumor necrosis factor (TNF) is a well-known cytokine that triggers insulin resistance during obesity development. On the other hand, it is also known that TNF induces a fat mass loss during acute diseases. However, whether TNF has a protective and physiological role to control adipose tissue expansion during obesity still needs to be verified. The aim of this study was to evaluate whether the ablation of TNF receptor 1 (TNFR1) alters fat mass and insulin resistance induced by a highly refined carbohydrate–containing (HC) diet. Male C57 BL/6 wild-type (WT) mice and TNFR1 knockout (TNFR1–/–) mice were fed with chow or with the HC diet for 16 wk. TNFR1–/– mice gained more body weight than the WT groups independent of the diet composition. TNFR1–/– mice fed with the chow diet showed higher adiposity, accompanied by higher serum leptin levels. However, these mice showed lower non-esterified fatty acid levels. Furthermore, TNFR1–/– mice had suppressed TNF, interleukin (IL)-6, and IL-10 levels in adipose tissue compared with WT mice. TNFR1–/– mice fed with the HC diet were protected from increased adiposity and glucose intolerance induced by the HC diet and exhibited lower serum resistin levels. TNF signaling appears to have a paradoxical role on metabolism. Ablation of TNFR1 leads to a reduction of inflammatory cytokines in adipose tissue that is accompanied by higher adiposity in mice fed with chow diet. However, when these mice are given the HC diet, the loss of TNFR1 improves insulin sensitivity and protects mice against additional fat mass. •Tumor necrosis factor (TNF) is an important cytokine involved in diet-induced adipose tissue expansion.•We evaluated the effect of TNF receptor 1 (TNFR1) in adipose tissue expansion and remodeling.•Absence of TNFR1 in the control reduces the content of cytokines in adipose tissue.•The near-ablation of cytokine levels is associated with higher adiposity.•A lack of TNFR1 protects mice from glucose intolerance induced by a high-carbohydrate diet.