Insulin resistance and adipose tissue interactions as the cornerstone of metabolic (dysfunction)-associated fatty liver disease pathogenesis.

The relationship between metabolic derangements and fatty liver development are undeniable, since more than 75% of patients with type 2 diabetes mellitus present with fatty liver. There is also significant epidemiological association between insulin resistance (IR) and metabolic (dysfunction)-associated fatty liver disease (MAFLD). For little more than 2 years, the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups. While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed, the bottom line relies on the role of IR as an initiator and perpetuator of this disease. There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations, where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory element-binding protein-1c induced lipogenic enzyme stimulation; therefore, increased endogenous production of triglycerides. The same effect is achieved through impaired suppression of adipose tissue (AT) lipolysis in insulin-resistant states, increasing fatty acid influx into the liver. The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion, modifying fatty acid metabolism as well as IR in a variety of tissues, including skeletal muscle, AT, and the liver. The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.