Adipose-specific VDR deletion leads to Hepatic steatosis in female mice fed a low fat diet

Risk factors for non-alcoholic hepatic steatosis include obesity and vitamin D deficiency which commonly co-exist. Thus, the role of vitamin D signaling in the prevention of hepatic steatosis in the absence of obesity or a “western” high fat diet is unclear. These studies were performed to address the role of the adipocyte Vitamin D Receptor (VDR) in the prevention of hepatic steatosis in mice fed a chow diet containing 5% fat by weight. Female mice with adipocyte VDR ablation (Adipoq-Cre; VDR flox/flox) exhibited a mild increase in weight gain at 70 days of age, accompanied by an increase in visceral adipose tissue (VAT) weight. While they did not exhibit evidence of hepatic inflammation or fibrosis, an increase in hepatic lipid content was observed. This was accompanied by an increase in the hepatic expression of genes involved in fatty acid transport and synthesis, as well as fatty acid oxidation. Markers of hepatic inflammation and fibrosis were unaffected by adipocyte VDR ablation. Consistent with the increase in VAT weight in the Adipoq-Cre; VDR flox/flox mice, higher levels of transcripts encoding adiopogenesis related genes were observed in VAT. In contrast to other models of impaired vitamin D signaling studied in the setting of a high fat or “western” diet, the Adipoq-Cre; VDR flox/flox mice do not exhibit hepatic inflammation or fibrosis. These findings suggest that the adipocyte VDR regulates hepatic lipid accumulation, but in the absence of obesity or a high fat diet, is not required to prevent hepatic inflammation or fibrosis.