Possible roles of growth factors and pancreatic hormones in the physiopathology of the non-alcoholic fatty liver disease

Abstract

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased paralleling with diabetes and metabolic syndrome. This trend has contributed to a surge in metabolic dysfunction–associated steatotic liver disease (MASLD), the most common chronic liver disease worldwide. NAFLD is defined by excessive triglycerides (TG) accumulation in hepatocytes, independent of alcohol consumption. Fatty liver arises from either increased TG delivery to the liver or carbohydrate conversion into TG. NAFLD shares key pathogenic mechanisms with metabolic syndrome, including obesity, hyperlipidemia, insulin resistance, mitochondrial dysfunction, oxidative stress, and inflammation. Two growth factors— Hepatocyte growth factor (HGF) and Epidermal growth factor (EGF)—may play significant roles in NAFLD pathophysiology. HGF interacts with insulin to regulate glucose metabolism in hepatocytes contributing to glucose homeostasis. EGF may also influence glucagon secretion by counteracting its suppression by plasma glucose, besides to be involved in liver cell proliferation. The known effects of these growth factors and hormones are largely loss at the onset of NAFLD. Therefore, this review explores the potential roles of HGF, EGF, and the pancreatic hormones insulin and glucagon in the NAFLD and evaluates their possible utility as biomarkers for diagnosis and therapeutic monitoring, since NAFLD, as an emerging disease, requires early detection and accurate prediction of disease progression for effective management.