Liver-specific RORα deletion does not affect the metabolic susceptibility to western style diet feeding

2019 
Abstract Objectives The nuclear receptor superfamily is a potential target for the development of new treatments for obesity and metabolic diseases. Increasing evidence has pointed towards the retinoic acid-related orphan receptor-alpha (RORα) as an important nuclear receptor involved in several biological processes. RORα full body knockout mice display improved metabolic phenotypes on both chow and high fat (60% fat, 20% carbohydrate) diets, but also have severe behavioral abnormalities. Here we investigated the effect of hepatic RORα by generating mice with liver-specific RORα deletion to elucidate the role of this nuclear receptor on host metabolism. Methods 8 week-old mice with liver-specific RORα deletion and littermate controls were fed either chow or western-style diets (40% fat, 40% carbohydrate) for 12 weeks. Metabolic phenotyping was performed at the end of the dietary intervention. Results Here, we show that hepatic RORα deletion does not affect the metabolic susceptibility to either chow or western-style diet in terms of glucose metabolism and adiposity. Conclusions Our data indicate that liver deletion of RORα does not have a pivotal role in the regulation of hepatic glucose and lipid metabolism on chow or western-style diet.
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