role of enpp1 on adipocyte maturationenpp1在脂肪细胞成熟的角色.pdfVIP

Role of ENPP1 on Adipocyte Maturation 3. 3. 2 1,2 1,2 Jian Liang , Mingui Fu , Ester Ciociola , Manisha Chandalia *, Nicola Abate * 1 Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America, 2 Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America, 3 Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, Florida, United States of America Background. It is recognized that the ability of adipose tissue to expand in response to energy excess, i.e. adipocyte maturation, is important in determining systemic abnormalities in glucose and lipid metabolism. Ectonucleotide pyropho- sphatase phosphodiesterase 1 (ENPP1, also known as PC-1) has been recently reported to be involved in the pathogenesis of insulin resistance and related diseases. However, its role on adipose tissue physiology as a mechanism of systemic insulin resistance is not understood. This study was performed to evaluate whether ENPP1 is regulated during adipogenesis and whether over-expression in adipocytes can affect adipocyte maturation, a potential novel mechanism of ENPP1-related insulin resistance. Methodology/Principal Findings. ENPP1 expression was found down-regulated during 3T3-L1 maturation, and over-expression of human ENPP1 in 3T3-L1 (pQCXIP-ENPP1 vector) resulted in adipocyte insulin resistance and in defective adipocyte maturation. Adipocyte maturation was more efficient in mesenchymal embryonal cells from ENPP1 knockout mice than from wild-type. Conclusions. We identify ENPP1 as a novel mechanism of defective adipocyte maturation. This mechanism could contribute to the patho