Adipose Tissue Invariant NKT Cells Protect Against Diet-Induced Obesity and Metabolic Disorder Through Regulatory Cytokine Production

Immunity. 2012 Sep 21;37(3):574-87. doi: 10.1016/j.immuni.2012.06.016. Epub 2012 Sep 13.

Abstract

Invariant natural killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in humans, were highly enriched in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells via their lipid ligand, alpha-galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty liver and improved insulin sensitivity through anti-inflammatory cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue / immunology*
  • Adipose Tissue / metabolism
  • Adoptive Transfer
  • Adult
  • Animals
  • Antigens, CD1d / genetics
  • Antigens, CD1d / immunology
  • Antigens, CD1d / metabolism
  • CD11c Antigen / immunology
  • CD11c Antigen / metabolism
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Diet, High-Fat / adverse effects
  • Female
  • Flow Cytometry
  • Humans
  • Liver / immunology
  • Liver / metabolism
  • Lymphocyte Count
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Metabolic Diseases / etiology
  • Metabolic Diseases / immunology*
  • Metabolic Diseases / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Obese
  • Middle Aged
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • Natural Killer T-Cells / transplantation
  • Obesity / etiology
  • Obesity / immunology*
  • Obesity / metabolism
  • Spleen / immunology
  • Spleen / metabolism
  • Young Adult

Substances

  • Antigens, CD1d
  • CD11c Antigen
  • Cd1d1 protein, mouse
  • Cytokines