| First Author | He S | Year | 2021 |
| Journal | J Clin Invest | Volume | 131 |
| Issue | 24 | PubMed ID | 34730111 |
| Mgi Jnum | J:321872 | Mgi Id | MGI:6871808 |
| Doi | 10.1172/JCI148545 | Citation | He S, et al. (2021) LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance. J Clin Invest 131(24):e148545 |
| abstractText | 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 beta-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. |
