Liqing Yu, MD PhD

Assistant Professor of Pathology -
Lipid Sciences; and Internal Medicine -
Cardiology

Faculty Profile
Tel: 336-716-0920
Fax: 336-716-6279
lyu@wakehealth.edu

• Director: Transgenic Mouse Core Facility
• Program Faculty:  Biochemistry
• Center/Institute Membership: Translational Science Institute

Current Research:

Project 1: NPC1L1 and Metabolic Diseases

Niemann-Pick C1-Like 1 (NPC1L1) protein is essential for cholesterol absorption from the gut lumen, a major pathway governing whole-body cholesterol homeostasis. It is the molecular target of a potent cholesterol-lowering drug ezetimibe (commercially known as Zetia). Unexpectedly, we and others found that mice lacking NPC1L1 or treated with ezetimibe are completely protected against high fat diet-induced obesity and fatty liver. We are currently probing how NPC1L1-dependent intestinal cholesterol absorption and ezetimibe modulate the pathogenesis of metabolic diseases such as obesity, fatty liver, and type 2 diabetes by using several genetically engineered mouse models and biochemical approaches.

Project 2: CGI-58 and Metabolic Diseases

Dysregulation of lipid metabolism is a hallmark of metabolic diseases such as fatty liver, obesity and diabetes, which contribute substantially to disease morbidity and mortality. A gene implicated in cellular fat balance is CGI-58 (Comparative Gene Identification-58), a lipid droplet-associated protein that is also known as abhd5 (a/b-hydrolase domain-containing 5). Mutations in human CGI-58 cause a neutral lipid storage disease, Chanarin-Dorfman syndrome that presents with ichthyosis (thickened dry skin) and accumulation of triglyceride-rich lipid droplets in most tissues. CGI-58 is ubiquitously expressed. CGI-58 appears to function as a coactivator of a triglyceride hydrolase in vitro. We found that CGI-58-driven triglyceride hydrolysis augments fatty acid oxidation and lipoprotein-lipid secretion in cultured hepatoma cells. CGI-58 may have similar functions in vivo. Interestingly, we observed that inhibition of CGI-58 in mice by antisense oligonucleotides causes severe fatty liver, but paradoxically and dramatically increases insulin sensitivity. Since whole-body CGI-58 knockout mice die shortly after birth due to a skin barrier defect, we have created CGI-58 floxed mice using the gene-targeting technology. After crossing with tissue-specific or inducible Cre enzyme-expressing mice, CGI-58 gene can be selectively deleted in a tissue-specific or inducible manner. We are currently using these animals to explore tissue-specific roles of CGI-58 in fat metabolism, insulin signaling, and inflammatory signaling.

Publications:

Coy C. Carpenter Library Publication Database