Diet‐induced obesity and non‐alcoholic fatty liver disease in TRPV1 null mice

The TRPV1 ion channel has been linked to metabolic homeostasis through a variety of proposed mechanisms including; control of appetite and weight, regulation of pancreatic function, thermogenesis, metabolism, and energy balance. Despite this, little information is known regarding its role in liver homeostasis. To better understand the role of TRPV1 in liver metabolism, we explored the effects of either a 24 week chow or high fat/sugar diet (Western, 42.7% carbohydrates, 42% fat, 15.2% protein, 0.2% cholesterol) regimen in male and female wild type (WT) and TRPV1‐null (V1KO) mice. Our data reveals that a loss of TRPV1 channel predisposes male mice to diet‐induced obesity and non‐alcoholic fatty liver disease (NAFLD). V1KO male mice on a western diet displayed numerous phenotypic changes associated with diet‐induced obesity, including increased body mass, adiposity, insulin resistance and glucose intolerance compared to their WT counterparts. Further, western diet fed male V1KO mice exhibited gross changes in liver morphology and size compared to western diet fed WT mice; which were visualized using histological H&E and Oil Red O staining. Moreover, western diet fed male V1KO mice exhibited significantly elevated triglyceride, cholesterol and free fatty acid liver lipid levels compared to western fed WT mice. Gene expression studies revealed decreases in CYP8B1, SREBP2 and HNFα1 gene expression as potential targets for further examination. Of note, western diet fed female V1KO mice were resistant to many of the diet‐induced changes in male counterparts. Taken together, these data demonstrate that loss of TRPV1 promotes fat accumulation, NAFLD development and severe changes in liver lipid profiles, while illustrating that TRPV1 presence is protective against NAFLD development in diet‐induced obesity.