Liver-specific induction of Abcg5 and Abcg8 stimulates reverse cholesterol transport in response to ezetimibe treatment.

Objective: Previous studies have shown ezetimibe treatment results in a 2-6-fold increase in reverse cholesterol transport (RCT). However, recent sterol balance studies question the role of biliary sterol secretion in RCT, and challenge the hypothesis that ezetimibe increases RCT through decreased absorption of biliary cholesterol in the intestine. We set out to determine whether ezetimibe may increase RCT by mechanisms that are independent of its well-established inhibition of intestinal cholesterol absorption.

Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.

Aims: Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we characterize the phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic changes induced by maternal diet in adult offspring.

Targeting of Acyl-CoA synthetase 5 decreases jejunal fatty acid activation with no effect on dietary long-chain fatty acid absorption.

Background: The absorption of dietary long chain fatty acids (LCFA) largely occurs in the jejunum. LCFA are activated via conjugation with Coenzyme A (CoA), a reaction catalyzed by Acyl-CoA synthetases (ACS). Acyl-CoA sythesis is critical for dietary LCFA absorption; yet, the jejunal ACS enzymes that catalyze the reaction are largely unknown.

Dysregulation of cholesterol homeostasis in human prostate cancer through loss of ABCA1.

Recent epidemiologic data show that low serum cholesterol level as well as statin use is associated with a decreased risk of developing aggressive or advanced prostate cancer, suggesting a role for cholesterol in aggressive prostate cancer development. Intracellular cholesterol promotes prostate cancer progression as a substrate for de novo androgen synthesis and through regulation of AKT signaling. By conducting next-generation sequencing-based DNA methylome analysis, we have discovered marked hypermethylation at the promoter of the major cellular cholesterol efflux transporter, ABCA1, in LNCaP prostate cancer cells.