Pathophysiology of Non Alcoholic Fatty Liver Disease

Abstract

The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation.

Identification of an intrinsic lysophosphatidic acid acyltransferase activity in the lipolytic inhibitor G 0 /G 1 switch gene 2 (G0S2)

“…Nonalcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease not related to alcohol consumption. NAFLD is developed when hepatic steatosis becomes sustained due to disruptions of the equilibrium between metabolic pathways for triacylglycerol (TG) synthesis, hydrolysis, and secretion (1)(2)(3)(4). The major sources of fatty acids (FAs) contributing to hepatic TG synthesis are the nonesterified FAs from adipose tissue, dietary FAs, and FAs derived from lipoprotein remnant, and newly synthesized FAs through de novo lipogenesis (DNL) (5,6).…”

Hepatic Zonation Now on Hormones!

“…Furthermore, the effect of fasting and feeding and of plasma ratios of glucagon to insulin, and plasma glucose levels on dynamic liver zonation, remains to be further investigated. Indeed, fasting serum levels of insulin and glucagon are increased in patients with various metabolic disorders, including type 2 diabetes and NASH . Their hepatic concentrations are much higher than in the periphery because the pancreas directly releases insulin and glucagon into the portal vein to the liver, whereas insulin and glucagon production, secretion, and response to the dietary glucose and lipids are perturbed in various metabolic diseases .…”

“…Indeed, fasting serum levels of insulin and glucagon are increased in patients with various metabolic disorders, including type 2 diabetes and NASH . Their hepatic concentrations are much higher than in the periphery because the pancreas directly releases insulin and glucagon into the portal vein to the liver, whereas insulin and glucagon production, secretion, and response to the dietary glucose and lipids are perturbed in various metabolic diseases . Given the similarity between the mouse and human liver zonation, comprehensive investigation of gastrointestinal hormone levels and their effect on metabolic liver zonation, using various mouse metabolic disease models, would be pertinent studies in this field.…”

Fimasartan Ameliorates Nonalcoholic Fatty Liver Disease through PPARδ Regulation in Hyperlipidemic and Hypertensive Conditions

“…Several examples are as follows: adiponectin treatment decreases the lipid accumulation in human macrophage cells [28], adiponectin regulates energy homeostasis through AMPK-ACC pathway [29], and adiponectin concentration in serum is lower in obese persons and patients with type 2 diabetes mellitus and NAFLD [30]. …”