What if Prometheus had steatosis? Potential use of FGF19 to promote regeneration of the fatty liver

Non-alcoholic fatty liver disease (NAFLD), the excess accumulation of triglycerides in the liver, can lead to liver-associated morbidity and mortality1 and is associated with extrahepatic disorders such as diabetes, obesity and increased cardiovascular risk. NAFLD is becoming extremely prevalent, estimated to affect 30%–45% of the population in the USA.2 ,3 Given this high prevalence, the impact of NAFLD has become important in other aspects of medical care; one such aspect is liver surgery. Patients with steatosis who undergo major hepatic resection are at an increased risk for perioperative complications and mortality,4 and the regeneration of the liver postresection is slower in the obese and those with NAFLD.5 ,6 Furthermore, in liver transplantation, steatotic grafts show decreased graft survival and function.7 Fibroblast growth factor 19 (FGF19) and its mouse ortholog Fgf15 are peptide hormones with myriad metabolic functions. Driven by luminal bile acid content and farnesoid X receptor, FGF15/19 is expressed in, and secreted from, the terminal ileum and closes the eneterohepatic feedback loop by acting on the liver to decrease hepatic bile acid synthesis. In addition, FGF15/19 regulates hepatic lipid and glucose metabolism, and affects energy expenditure and food …