Conclusions
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.
Methods
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.
Results
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. Conclusions: 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.