Prolactin improves hepatic steatosis via CD36 pathway

[Display omitted] •Circulating prolactin levels are negatively associated with the development of NAFLD.•Prolactin receptor expression is decreased in livers of obese patients in the presence of NAFLD.•Prolactin/prolactin receptor improved hepatic steatosis via suppression of hepatic CD36. Prolactin (PRL) is a multifunctional polypeptide with effects on metabolism, however, little is known about its effect on hepatic steatosis and lipid metabolism. Herein, we aimed to assess the role of PRL in the development of non-alcoholic fatty liver disease (NAFLD). The serum PRL levels of 456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and 85 individuals with liver histology obtained during metabolic surgery (44 female and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals) were evaluated. The expression of the gene encoding the prolactin receptor (PRLR) and signalling molecules involved in hepatic lipid metabolism were evaluated in human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were tested in free fatty acid (FFA)-treated HepG2 cells. Circulating PRL levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9 [range, 5.9–10.3] µg/L; women: 8.7 [range, 6.1–12.4] µg/L) than those with non-NAFLD (men: 9.1 [range, 6.8–13.0] µg/L, p = 0.002; women: 11.6 [range, 8.2–16.1] µg/L, p