Mice lacking natural killer T cells are more susceptible to metabolic alterations following high fat diet feeding.
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.
Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Brittany V
BV
Martin-Murphy
Department 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.
Qiang
Q
You
Division of Endocrinology, Diabetes & Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Hong
H
Wang
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Becky A
BA
De La Houssaye
Drug Safety Evaluation, Research & Development, Bristol-Myers Squibb Company, Princeton, New Jersey, United States of America.
Timothy P
TP
Reilly
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Jacob E
JE
Friedman
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Cynthia
C
Ju
D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism; D002153:Calorimetry, Indirect; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000502:physiology; D009765:Obesity / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D055610:Antigens, CD1d; D012333:RNA, Messenger