Deletion of the transmembrane transporter ABCG1 results in progressive pulmonary lipidosis.

We show that mice lacking the ATP-binding cassette transmembrane transporter ABCG1 show progressive and age-dependent severe pulmonary lipidosis that recapitulates the phenotypes of different respiratory syndromes in both humans and mice. The lungs of chow-fed Abcg1(-/-) mice, >6-months old, exhibit extensive subpleural cellular accumulation, macrophage, and pneumocyte type 2 hypertrophy, massive lipid deposition in both macrophages and pneumocytes and increased levels of surfactant. No such abnormalities are observed at 3 months of age.

FXR deficiency causes reduced atherosclerosis in Ldlr-/- mice.

Objective: Based on the observation that Fxr-/- mice exhibit a proatherogenic lipoprotein profile, we investigated the role of FXR in the development of atherosclerosis.

Methods And Results: Administration of a western diet to Fxr-/- mice or wild-type mice does not result in the development of significant atherosclerotic lesions. Consequently we generated Fxr-/- Ldlr-/- (DKO) mice and compared lesion development with Ldlr-/- mice.

Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice.

Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic overexpression of constitutively active FXR by adenovirus-mediated gene transfer significantly lowered blood glucose levels in both diabetic db/db and wild-type mice.