Deletion of TNFα receptor ‐1 and 2 exacerbates trans‐10, cis‐ 12 CLA induced hepatic steatosis in the mouse

Abstract

Chronic intake of trans‐10, cis‐12 conjugated linoleic acid (t10, c12 CLA) causes detrimental effects such as lipid accumulation in liver and increased expression of the pro‐inflammatory cytokine tumor necrosis factor alpha (TNFα) in adipose tissue depots. TNFα is involved in dysregulation of hepatic lipid metabolism and insulin signaling. The role of TNFα in mediating the stimulatory effects of t10, c12 CLA on lipid accumulation in liver is unclear. To examine this issue, wild type C57BL/6J female mice (WT) and their counterparts lacking both TNFα receptor‐1 and 2 (TNFRKO) were fed diets containing 0.5% of either oleic acid or t10, c12 CLA for 2 weeks. As expected, t10, c12 CLA reduced adipose tissue mass and caused hyperinsulinemia and hepatic steatosis in WT mice. Hepatic steatosis in WT mice was associated with increased expression of many enzymes involved in lipogenesis. Surprisingly, the effects of t10, c12 CLA in TNFRKO liver were maintained for lipogenic gene expression and exacerbated for steatosis. We conclude that the effects of t10, c12 CLA on hepatic lipid metabolism do not require TNFα signaling.