Hepatocyte Retinoid X Receptor-α-Deficient Mice Have Reduced Food Intake, Increased Body Weight, and Improved Glucose Tolerance

Hepatocyte retinoid X receptor (RXR)α-deficient mice and wild-type mice were fed either a regular or a high-saturated-fat diet for 12 wk to study the functional role of hepatocyte RXRα in fatty acid and carbohydrate metabolism. Food intake was significantly reduced in hepatocyte RXRα-deficient mice when either diet was used. The amount of food intake was negatively associated with serum leptin level. Although mutant mice ate less, body weight and fat content were significantly higher in mutant than wild-type mice. Examination of the expression of peroxisome proliferator-activated receptor-α target genes indicated that the peroxisome proliferator-activated receptor-α-mediated pathway was compromised in the mutant mice, which, in turn, might affect fatty-acid metabolism and result in increased body weight and fat content. Although mutant mice were obese, they demonstrated the same degree of insulin sensitivity and the same level of serum insulin as the wild-type mice. However, these mutant mice have improve...