Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance

Masashi Satoh, Yasuhiro Andoh, Christopher Stuart Clingan, Hisako Ogura, Satoshi Fujii, Koji Eshima, Toshinori Nakayama, Masaru Taniguchi, Noriyuki Hirata, Naoki Ishimori, Hiroyuki Tsutsui, Kazunori Onoé, Kazuya Iwabuchi

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

The progression of obesity is accompanied by a chronic inflammatory process that involves both innate and acquired immunity. Natural killer T (NKT) cells recognize lipid antigens and are also distributed in adipose tissue. To examine the involvement of NKT cells in the development of obesity, C57BL/6 mice (wild type; WT), and two NKT-cell-deficient strains, Jα18 -/- mice that lack the type I subset and CD1d -/- mice that lack both the type I and II subsets, were fed a high fat diet (HFD). CD1d -/- mice gained the least body weight with the least weight in perigonadal and brown adipose tissue as well as in the liver, compared to WT or Jα18 -/- mice fed an HFD. Histologically, CD1d -/- mice had significantly smaller adipocytes and developed significantly milder hepatosteatosis than WT or Jα18 -/- mice. The number of NK1.1 +TCRβ + cells in adipose tissue increased when WT mice were fed an HFD and were mostly invariant Vα14Jα18-negative. CD11b + macrophages (Mφ) were another major subset of cells in adipose tissue infiltrates, and they were divided into F4/80 high and F4/80 low cells. The F4/80 low-Mφ subset in adipose tissue was increased in CD1d -/- mice, and this population likely played an anti-inflammatory role. Glucose intolerance and insulin resistance in CD1d -/- mice were not aggravated as in WT or Jα18 -/- mice fed an HFD, likely due to a lower grade of inflammation and adiposity. Collectively, our findings provide evidence that type II NKT cells initiate inflammation in the liver and adipose tissue and exacerbate the course of obesity that leads to insulin resistance.

Original languageEnglish
Article numbere30568
JournalPloS one
Volume7
Issue number2
DOIs
Publication statusPublished - Feb 22 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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