Insulin Resistance and Non-Alcoholic Fatty Liver Disease

Abstract

Insulin resistance plays a critical role in a number of metabolic diseases, such as metabolic syndrome, type 2 diabetes mellitus (T2DM), and steatotic liver disease. It is mainly driven by chronic low-grade inflammation in white adipose tissue (WAT), which functions as an endocrine organ secreting a plethora of signaling molecules, bioactive lipids, and inflammatory adipokines that modify insulin sensitivity. A key consequence of this metabolic environment is the development of metabolic-dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD). Accumulation of lipids within the hepatocytes (steatosis) is the first stage of MASLD, which may lead to steatohepatitis, fibrosis, and eventually to cirrhosis and hepatocellular carcinoma.