Obesity, Inflammation, and Insulin Resistance Steven E. Shoelson, Laura Herrero, Afia Naaz  Gastroenterology  Volume 132, Issue 6, Pages 2169-2180 (May 2007) DOI: 10.1053/j.gastro.2007.03.059 Copyright © 2007 AGA Institute Terms and Conditions

Figure 1 Potential mechanisms for inflammation-induced injury in NAFLD. Multiple cell types within the hepatic sinusoid, including hepatocytes, endothelial cells, hepatic stellate cells (HSC), resident macrophages (Kupffer cells), B and T lymphocytes, NK cells, NKT cells and dentritic cells (DCs), may contribute to the inflammatory processes that accompany steatosis. Stellate cells are often found in the subendothelial space of Disse. The immune cells including the Kupffer cells line the sinusoid lumen. The portal delivery of lipids and proinflammatory cytokines as well as locally generated inflammatory mediators and reactive oxygen species may promote both inflammatory and fibrotic processes associated with the progression of NAFLD. Gastroenterology 2007 132, 2169-2180DOI: (10.1053/j.gastro.2007.03.059) Copyright © 2007 AGA Institute Terms and Conditions

Figure 2 Adipose tissue inflammation. H&E-stained sections are shown from the epididymal adipose tissue of 14-week-old (A) wt C57Bl/6 mice and (B) obese ob/ob mice. The increase in fat cell size seen in ob/ob mice is accompanied by the increased infiltration of immune cells including macrophages (arrows). Gastroenterology 2007 132, 2169-2180DOI: (10.1053/j.gastro.2007.03.059) Copyright © 2007 AGA Institute Terms and Conditions

Figure 3 Potential mechanisms for obesity-induced inflammation. The accumulation of lipids in adipose tissue and the expansion of the fat mass lead to the initiation of an inflammatory process. This may be initiated through the production of proinflammatory cytokines and chemokines by the adipocytes, including TNF-α, IL-6, leptin, resistin, MCP-1, and PAI-1. Endothelial cells respond through the increased expression of adhesion molecules, which along with the chemokines serve to recruit immune cells including monocyte-derived macrophages to the adipose tissue. Together, the adipocyte-, immune cell-, and endothelial cell-derived substances create an inflammatory milieu that promotes insulin resistance locally. Similar proinflammatory and proatherogenic mediators enter the circulation to promote insulin resistance and increase risk for atherosclerosis. Gastroenterology 2007 132, 2169-2180DOI: (10.1053/j.gastro.2007.03.059) Copyright © 2007 AGA Institute Terms and Conditions

Steven Shoelson, MD, PhD Gastroenterology 2007 132, 2169-2180DOI: (10.1053/j.gastro.2007.03.059) Copyright © 2007 AGA Institute Terms and Conditions