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.