3-Hydroxyacyl-CoA dehydratase 2 deficiency confers resistance to diet-induced obesity and glucose intolerance.

Obesity and associated complications are becoming a pandemic. Inhibiting fatty acid synthesis and elongation is an important intervention for the treatment of obesity. Despite intensive investigations, many potential therapeutic targets have yet to be discovered. In this study, decreased expression of Hacd2 (a newly found enzyme in fatty acid elongation) was found in HFD induced mice and loss of Hacd2 expression in the liver protected mice against HFD induced obesity as well as associated fatty liver disease and diabetes. Additionally, further study indicated that hepatic HACD2 deficiency increased energy expenditure by upregulating the transcription of thermogenic programming genes. Our results suggest that HACD2 may be a promising therapeutic target for the management of obesity and associated metabolic diseases.