School of Medicine Publications and Presentations
Document Type
Article
Publication Date
12-15-2021
Abstract
Dysregulation in adipokine biosynthesis and function contributes to obesity-induced metabolic diseases. However, the identities and functions of many of the obesity-induced secretory molecules remain unknown. Here, we report the identification of leucine-rich alpha-2-glycoprotein 1 (LRG1) as an obesity-associated adipokine that exacerbates high fat diet–induced hepatosteatosis and insulin resistance. Serum levels of LRG1 were markedly elevated in obese humans and mice compared with their respective controls. LRG1 deficiency in mice greatly alleviated diet-induced hepatosteatosis, obesity, and insulin resistance. Mechanistically, LRG1 bound with high selectivity to the liver and promoted hepatosteatosis by increasing de novo lipogenesis and suppressing fatty acid β-oxidation. LRG1 also inhibited hepatic insulin signaling by downregulating insulin receptor substrates 1 and 2. Our study identified LRG1 as a key molecule that mediates the crosstalk between adipocytes and hepatocytes in diet-induced hepatosteatosis and insulin resistance. Suppressing LRG1 expression and function may be a promising strategy for the treatment of obesity-related metabolic diseases.
Recommended Citation
He, S., Ryu, J., Liu, J., Luo, H., Lv, Y., Langlais, P. R., Wen, J., Dong, F., Sun, Z., Xia, W., Lynch, J. L., Duggirala, R., Nicholson, B. J., Zang, M., Shi, Y., Zhang, F., Liu, F., Bai, J., & Dong, L. Q. (2021). LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance. The Journal of clinical investigation, 131(24), e148545. https://doi.org/10.1172/JCI148545
Publication Title
The Journal of Clinical Investigation
DOI
10.1172/JCI148545
Academic Level
faculty
Mentor/PI Department
Office of Human Genetics
Comments
© 2021, American Society for Clinical Investigation. Original published version available at https://doi.org/10.1172/JCI148545