Identification and characterization of a novel gene faci that alleviates highfat diet-induced metabolic syndrome in mice

Abstract

Metabolic syndrome refers to a cluster of metabolic abnormalities with increased risk for diabetes and cardiovascular diseases. The metabolic abnormalities include insulin resistance, dyslipidemia, abdominal obesity and hypertension. Genetic factors are known to contribute to the development of metabolic syndrome. However, the identity of genes that govern insulin resistance and hyperlipidemia remains incompletely understood. Here we identified and characterized a novel gene named Faci (fasting and CREB induced gene), which exhibits anti-insulin resistance and antihyperlipidemic effects. Faci is highly expressed in the intestine and the liver, and moderately expressed in the adrenal gland and the adipose tissue. The promoter of Faci gene was identified and characterized. Multiple metabolic related stimuli, such as fasting, CREB-CRTC2 and PGC1α, were found to induce Faci transcription. Liver-specific Faci transgenic expression by adenoassociated virus (AAV) protects C57B6J mice from high-fat diet-induced insulin resistance. Hepatic Faci-overexpressed mice also exhibit lower blood LDL-c (low-density lipoprotein cholesterol) after high-fat-diet feeding. Intracellular staining indicated that Faci localizes to the proximity of lipid vesicles in hepatic HepG2 cells, suggesting a role in lipid metabolism. To sum up, this is the first report of Faci, a novel gene involved in lipid metabolism. Full characterization of Faci might reveal its role in the pathogenesis of metabolic syndrome and provide a promising new target for its prevention and intervention. Supported by HMRF 05163786.