title: Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance.
abstract: 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.
  
  
  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 NH(2)-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.
authors.affiliation: Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
authors.forename: Yun Sok
authors.initials: YS
authors.lastname: Lee
authors.forename: Pingping
authors.initials: P
authors.lastname: Li
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Huh
authors.forename: In Jae
authors.initials: IJ
authors.lastname: Hwang
authors.forename: Min
authors.initials: M
authors.lastname: Lu
authors.forename: Jong In
authors.initials: JI
authors.lastname: Kim
authors.forename: Mira
authors.initials: M
authors.lastname: Ham
authors.forename: Saswata
authors.initials: S
authors.lastname: Talukdar
authors.forename: Ai
authors.initials: A
authors.lastname: Chen
authors.forename: Wendell J
authors.initials: WJ
authors.lastname: Lu
authors.forename: Guatam K
authors.initials: GK
authors.lastname: Bandyopadhyay
authors.forename: Reto
authors.initials: R
authors.lastname: Schwendener
authors.forename: Jerrold
authors.initials: J
authors.lastname: Olefsky
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D002518:Ceramides / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004822:Epididymis / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002518:Ceramides; D004041:Dietary Fats; D005947:Glucose