TY - JOUR
T1 - Adipose Tissue Invariant NKT Cells Protect against Diet-Induced Obesity and Metabolic Disorder through Regulatory Cytokine Production
AU - Lynch, Lydia
AU - Nowak, Michael
AU - Varghese, Bindu
AU - Clark, Justice
AU - Hogan, Andrew E.
AU - Toxavidis, Vasillis
AU - Balk, Steven P.
AU - O'Shea, Donal
AU - O'Farrelly, Cliona
AU - Exley, Mark A.
N1 - R01 DK066917, NIDDK NIH HHS, United StatesR21 CA143748, NCI NIH HHS, United StatesR21 CA143748, NCI NIH HHS, United StatesR21 CA170194, NCI NIH HHS, United StatesU19 AI066313, NIAID NIH HHS, United States
PY - 2012/9/21
Y1 - 2012/9/21
N2 - 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. © 2012 Elsevier Inc.
AB - 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. © 2012 Elsevier Inc.
U2 - 10.1016/j.immuni.2012.06.016
DO - 10.1016/j.immuni.2012.06.016
M3 - Article
C2 - 22981538
SN - 1074-7613
VL - 37
SP - 574
EP - 587
JO - Immunity
JF - Immunity
IS - 3
ER -
