High-Fat Diet Induces Distinct Metabolic Response in Interleukin-6 and Tumor Necrosis Factor- Knockout Mice

Studies suggest interleukin-6 (IL-6) and tumor necrosis factor- (TNF-) may be beneficial in obesity-related disorders with inconsistent results. This study was designed to investigate and compare their pathophysiological roles in lipid metabolism with gene knockout approach. Male wild-type (WT), IL-6 knockout (IL-6(-/-)), and TNF- knockout (TNF-(-/-)) mice were maintained on either a chow diet or a high-fat diet (HFD) for 12 weeks. Indices of lipid metabolism in blood, adipose, and liver were determined. Our data showed that IL-6(-/-) and TNF-(-/-) mice were more pronounced in body weight gains, hypercholesterolemia, fasting and post-load hyperglycemia on a chow diet or a HFD compared with WT mice. In WT mice feeding on a HFD, lipolysis and glyceroneogenesis were enhanced, lipogenesis was inhibited in adipose tissue; lipogenesis was increased in liver tissue. IL-6(-/-) mice on a chow diet or a HFD showed similar metabolic phenotypes as WT mice on a HFD, since those mice had similar expression profiles of lipid-related genes in adipose tissue and liver. However, TNF-(-/-) mice were different. Therefore, IL-6(-/-) and TNF-(-/-) mice showed different hepatic triglyceride infiltration in response to different diets. Our study suggests that complete blockage of IL-6 and TNF- is unbeneficial in obesity and obesity-related metabolic disorders in mice.