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PLoS One. 2014 Jan 20;9(1):e80949. doi: 10.1371/journal.pone.0080949. eCollection 2014.

Mice lacking natural killer T cells are more susceptible to metabolic alterations following high fat diet feeding.

Author information

  • 1Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
  • 2Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
  • 3Division of Endocrinology, Diabetes & Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
  • 4Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
  • 5Drug Safety Evaluation, Research & Development, Bristol-Myers Squibb Company, Princeton, New Jersey, United States of America.
  • 6Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.

Abstract

Current estimates suggest that over one-third of the adult population has metabolic syndrome and three-fourths of the obese population has non-alcoholic fatty liver disease (NAFLD). Inflammation in metabolic tissues has emerged as a universal feature of obesity and its co-morbidities, including NAFLD. Natural Killer T (NKT) cells are a subset of innate immune cells that abundantly reside within the liver and are readily activated by lipid antigens. There is general consensus that NKT cells are pivotal regulators of inflammation; however, disagreement exists as to whether NKT cells exert pathogenic or suppressive functions in obesity. Here we demonstrate that CD1d(-/-) mice, which lack NKT cells, were more susceptible to weight gain and fatty liver following high fat diet (HFD) feeding. Compared with their WT counterparts, CD1d(-/-) mice displayed increased adiposity and greater induction of inflammatory genes in the liver suggestive of the precursors of NAFLD. Calorimetry studies revealed a significant increase in food intake and trends toward decreased metabolic rate and activity in CD1d(-/-) mice compared with WT mice. Based on these findings, our results suggest that NKT cells play a regulatory role that helps to prevent diet-induced obesity and metabolic dysfunction and may play an important role in mechanisms governing cross-talk between metabolism and the immune system to regulate energy balance and liver health.

PMID:
24465369
[PubMed - indexed for MEDLINE]
PMCID:
PMC3896335
Free PMC Article
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