['Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme in the bile acid biosynthetic pathway that converts cholesterol into bile acids in the liver. Recent studies have shown that bile acids may play an important role in maintaining lipid, glucose, and energy homeostasis. However, the role of CYP7A1 in the development of obesity and diabetes is currently unclear. In this study, we demonstrated that transgenic mice overexpressing Cyp7a1 in the liver [i.e., Cyp7a1 transgenic (Cyp7a1-tg) mice] were resistant to high-fat diet (HFD)-induced obesity, fatty liver, and insulin resistance. Cyp7a1-tg mice showed increased hepatic cholesterol catabolism and an increased bile acid pool. Cyp7a1-tg mice had increased secretion of hepatic very low density lipoprotein but maintained plasma triglyceride homeostasis. Gene expression analysis showed that the hepatic messenger RNA expression levels of several critical lipogenic and gluconeogenic genes were significantly decreased in HFD-fed Cyp7a1-tg mice. HFD-fed Cyp7a1-tg mice had increased whole body energy expenditure and induction of fatty acid oxidation genes in the brown adipose tissue.'] Does transgenic expression of cholesterol 7alpha-hydroxylase in the liver prevent high-fat diet-induced obesity and insulin resistance in mice?