Lipocalin 13 regulation of glucose and lipid metabolism in obesity

Lipocalin (LCN) family members are small secreted proteins that bind to small hydrophobic molecules via their characteristic central β-barrels. A couple of LCN family members, including major urinary protein 1, retinol-binding protein 4, LCN2, and LCN13, have been reported to regulate insulin sensitivity and nutrient metabolism. LCN13 is expressed by multiple tissues, including the liver, pancreas, epididymis, and skeletal muscle, and is secreted into the bloodstream in mice. Obesity is associated with a downregulation of LCN13 expression and lower levels of circulating LCN13. LCN13 therapies overcome LCN13 deficiency in mice with either genetic or dietary obesity, leading to an improvement in hyperglycemia, hyperinsulinemia, insulin resistance, glucose intolerance, and hepatic steatosis. In hepatocytes, LCN13 directly suppresses hepatic gluconeogenesis and lipogenesis but increases fatty acid β oxidation. LCN13 also enhances insulin sensitivity in adipocytes. The potential mechanisms of the antidiabetes and antisteatosis actions of LCN13 are discussed.