RT Journal Article SR Electronic T1 Inflammation Is Necessary for Long-Term but Not Short-Term High-Fat Diet–Induced Insulin Resistance JF Diabetes JO Diabetes FD American Diabetes Association SP 2474 OP 2483 DO 10.2337/db11-0194 VO 60 IS 10 A1 Lee, Yun Sok A1 Li, Pingping A1 Huh, Jin Young A1 Hwang, In Jae A1 Lu, Min A1 Kim, Jong In A1 Ham, Mira A1 Talukdar, Saswata A1 Chen, Ai A1 Lu, Wendell J. A1 Bandyopadhyay, Guatam K. A1 Schwendener, Reto A1 Olefsky, Jerrold A1 Kim, Jae Bum YR 2011 UL http://diabetes.diabetesjournals.org/content/60/10/2474.abstract AB OBJECTIVE Tissue inflammation is a key factor underlying insulin resistance in established obesity. Several models of immuno-compromised mice are protected from obesity-induced insulin resistance. However, it is unanswered whether inflammation triggers systemic insulin resistance or vice versa in obesity. The purpose of this study was to assess these questions.RESEARCH DESIGN AND METHODS We fed a high-fat diet (HFD) to wild-type mice and three different immuno-compromised mouse models (lymphocyte-deficient Rag1 knockout, macrophage-depleted, and hematopoietic cell-specific Jun NH2-terminal kinase–deficient mice) and measured the time course of changes in macrophage content, inflammatory markers, and lipid accumulation in adipose tissue, liver, and skeletal muscle along with systemic insulin sensitivity.RESULTS In wild-type mice, body weight and adipose tissue mass, as well as insulin resistance, were clearly increased by 3 days of HFD. Concurrently, in the short-term HFD period inflammation was selectively elevated in adipose tissue. Interestingly, however, all three immuno-compromised mouse models were not protected from insulin resistance induced by the short-term HFD. On the other hand, lipid content was markedly increased in liver and skeletal muscle at day 3 of HFD.CONCLUSIONS These data suggest that the initial stage of HFD-induced insulin resistance is independent of inflammation, whereas the more chronic state of insulin resistance in established obesity is largely mediated by macrophage-induced proinflammatory actions. The early-onset insulin resistance during HFD feeding is more likely related to acute tissue lipid overload.