The role of hepatic and adipose tissues cyclic adenosine monophosphate during the development of experimental non alcoholic fatty liver

Abstract

Nonalcoholic fatty liver disease (NAFLD), first identified in 1980, is a global public health issue due to its growing worldwide prevalence and potentially severe consequences. NAFLD is a group of hepatic disorders characterized by macrovesicular steatosis that occurs when there is no alcohol intake. The histologic spectrum of NAFLD includes simple steatosis, which has a benign prognosis, and NASH which may be complicated by progressive fibrosis and cirrhosis. NAFLD is recognized as the major cause of liver-related morbidity and mortality. An interesting working model known as the “two-hit” model postulates that the progression from simple NASH, fibrosis, or cirrhosis occurs through two steps or hits. The “first hit” is excessive accumulation of hepatocyte triglycerides that can result from insulin resistance (IR). The presumed factors initiating a second hit are suggested to be oxidative stress and subsequent lipid peroxidation and proinflammatory cytokines. Moreover, a further component, or ‘third-hit’ has been added to reflect inadequate hepatocyte proliferation. Oxidative stress decreases the mature