Abrogation of GH action in Kupffer cells results in increased hepatic CD36 expression and exaggerated nonalcoholic fatty liver disease

To investigate the effects of GH signaling on Kupffer cells and the resulting changes in lipid homeostasis and their underlying mechanism(s) in the livers of diet-induced obese (DIO) mice. Male macrophage specific-growth hormone receptor knockout mice (MacGHR KO) and their litter mate controls were fed a high fat diet containing 60% calories from fat for 26 weeks. Lipid content and lipid profiles in the liver and circulation were analyzed. Expression levels of CD36 in the liver were quantified by RT-PCR and Western Blot. Increased hepatic lipid content and abundance of long-chain unsaturated fatty acids were observed in the liver of MacGHR KO mice. These findings were associated with increased steady state levels of CD36 mRNA and protein in MacGHR KO mice when compared with their litter mate controls. GH action in Kupffer cells is required for maintaining hepatic lipid homeostasis, in part via regulation of hepatic CD36 expression. •Our findings indicate that GH action in Kupffer cells is required for maintaining hepatic lipid homeostasis.•Our results support a model that in DIO, lack of GH action on KCs results in increased lipid deposition in the liver mediated by increased CD36 expression.•We conclude that one of the physiological roles of GH on KC is to suppress CD36 expression in the liver.