Volume 142, Issue 4, Pages 711-725.e6 (April 2012) Role of Obesity and Lipotoxicity in the Development of Nonalcoholic Steatohepatitis: Pathophysiology and Clinical Implications  Kenneth Cusi  Gastroenterology  Volume 142, Issue 4, Pages 711-725.e6 (April 2012) DOI: 10.1053/j.gastro.2012.02.003 Copyright © 2012 AGA Institute Terms and Conditions

Figure 1 Obesity and triglyceride-derived toxic lipid metabolites accumulate in ectopic tissues and lead to multiorgan dysfunction and common chronic metabolic diseases such as NAFLD and to T2DM and CVD. Gastroenterology 2012 142, 711-725.e6DOI: (10.1053/j.gastro.2012.02.003) Copyright © 2012 AGA Institute Terms and Conditions

Figure 2 (A) Adipose tissue is composed of adipocytes and the stromal vascular fraction that includes macrophages and other immune cells that have a relevant role in the autocrine-paracrine regulation of adipocytes. In obesity, activation of macrophages/immune system contributes to the development of dysfunctional, insulin-resistant adipocytes that release excessive amounts of FFA and cause insulin resistance and lipoapoptosis in distant tissues (liver, muscle, pancreatic beta cells, vascular bed, other). Accumulation of triglyceride-derived toxic lipid metabolites activates intracellular inflammatory pathways within hepatocytes and Kupffer and other immune cells, in resemblance to defects within adipocytes. Activation of hepatic stellate cells leads to collagen deposition and the potential for cirrhosis. (B) PPAR-γ are widely distributed among adipocytes, hepatocytes, and hepatic stellate cells, as well as macrophages and immune cells infiltrating adipose and liver tissue that may be targeted by PPAR-γ agonists during TZD therapy in patients with NASH. Gastroenterology 2012 142, 711-725.e6DOI: (10.1053/j.gastro.2012.02.003) Copyright © 2012 AGA Institute Terms and Conditions

Figure 3 Schematic representation of the pathophysiology of NASH (see text for details). Gastroenterology 2012 142, 711-725.e6DOI: (10.1053/j.gastro.2012.02.003) Copyright © 2012 AGA Institute Terms and Conditions

Figure 4 CV risk factors that coexist in patients with NAFLD (see text for details). Gastroenterology 2012 142, 711-725.e6DOI: (10.1053/j.gastro.2012.02.003) Copyright © 2012 AGA Institute Terms and Conditions