Inflammation and fibrogenesis in steatohepatitis

Abstract

Nonalcoholic fatty liver disease consists of a range of disorders characterized by excess accumulation of triglyceride within the liver. Whereas simple steatosis is clinically benign, nonalcoholic steatohepatitis (NASH) often progresses to cirrhosis. Inflammation and fibrogenesis are closely inter-related and are major targets of NASH research. Experimental data have shown that inflammation in NASH is caused by insulin resistance, systemic lipotoxicity due to overnutrition, lipid metabolites, the production of proinflammatory cytokines and adipokines by visceral adipose tissue, gut-derived bacteria, and oxidative stress. In NASH-associated fibrosis, the principal cell type responsible for extracellular matrix production is recognized as the hepatic stellate cell. Although the fibrotic mechanisms underlying NASH are largely similar to those observed in other chronic liver diseases, the altered patterns of circulating adipokines, the generation of oxidative stress, and the hormonal profile associated with the metabolic syndrome might play unique roles in the fibrogenesis associated with the disease. Information on the basic pathogenesis of NASH with a focus on the generation of inflammation and fibrosis will be discussed.

Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the liver [Review]

“…HSC is a key player in hepatic regeneration and progression of fibrosis [58]. Activation of HSCs into the myofibroblast phenotype can be provoked by a range of chronic injuries to the liver including oxidative stress, inflammatory cytokines, and lipopolysaccharide (LPS) [59]. In cultured HSCs, IGF-I increases proliferation [60] and collagen synthesis [61].…”

Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity

“…Lipotoxicity and inflammation have been shown to induce cellular stress, resulting in altered tissue function (9,16,48,76). Such changes in placental development and/or function may have detrimental consequences on fetal metabolism.…”

The Riddle of Nonalcoholic Fatty Liver Disease: Progression From Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis

“…107 Hepatic stellate cells (HSCs) trans-differentiate from quiescent to active state under the influence of activators like platelet-derived growth factor (PDGF) and transforming growth factor b1 (TGF-b1) secreted by activated KC, infiltrating monocytes, platelets, and damaged hepatocytes. 108 The resting HSCs may acquire adipogenic or myogenic phenotype during the trans-differentiation, 109 determined by adipogenic and myogenic gene expression. Indubitably, adipogenic genes are down-regulated under ischemia and inflammation and up-regulated by peroxisome proliferator-activated receptor-g (PPAR-g).…”