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Int. J. Mol. Sci. 2018, 19(2), 510; https://doi.org/10.3390/ijms19020510

Deficiency of Invariant Natural Killer T Cells Does Not Protect Against Obesity but Exacerbates Atherosclerosis in Ldlr−/− Mice

1
Diabetes Obesity Center for Excellence, Division of Metabolism, Endocrinology and Nutrition, University of Washington, 850 Republican Street Box 35805, Seattle, WA 98109, USA
2
Division of Cardiology, University of Washington, Seattle, WA 98195, USA
3
Department of Pathology, University of Chicago, Chicago, IL 60637, USA
*
Author to whom correspondence should be addressed.
Received: 28 December 2017 / Revised: 27 January 2018 / Accepted: 29 January 2018 / Published: 8 February 2018
(This article belongs to the Special Issue Natural Killer T (NKT) Cells)
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Abstract

Obesity is a chronic inflammatory state characterized by altered levels of adipose tissue immune cell populations. Natural killer T (NKT) cells are CD1d restricted lymphocyte subsets that recognize lipid antigens whose level decreases in obese adipose tissue. However, studies in mice with deficiency or increased levels of NKT cells have yielded contradictory results, so the exact role of these cells in obesity and adipose tissue inflammation is not yet established. We previously showed that Ldlr−/− mice with excess invariant NKT (iNKT) cells demonstrate significant weight gain, adiposity, metabolic abnormalities, and atherosclerosis. The current study evaluates the effects of NKT cell deficiency on obesity, associated metabolic changes, and atherosclerosis in Jα18−/−Ldlr−/− (lacking iNKT cells) and Cd1d−/−Ldlr−/− (lacking invariant and type II NKT cells) mice, and control mice were fed an obesogenic diet (high fat, sucrose, cholesterol) for 16 weeks. Contrary to expectations, Ja18−/−Ldlr−/− mice gained significantly more weight than Ldlr−/− or Cd1d−/−Ldlr−/− mice, developed hypertriglyceridemia, and had worsened adipose tissue inflammation. All the mice developed insulin resistance and hepatic triglyceride accumulation. Ja18−/−Ldlr−/− mice also had increased atherosclerotic lesion area. Our findings suggest that iNKT cells exacerbates the metabolic, inflammatory, and atherosclerotic features of diet-induced obesity. Further work is required to unravel the paradox of an apparently similar effect of iNKT cell surplus and depletion on obesity. View Full-Text
Keywords: natural killer T cells; adipose tissue; atherosclerosis; inflammation natural killer T cells; adipose tissue; atherosclerosis; inflammation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Subramanian, S.; Goodspeed, L.; Wang, S.; Ding, Y.; O’Brien, K.D.; Getz, G.S.; Chait, A.; Reardon, C.A. Deficiency of Invariant Natural Killer T Cells Does Not Protect Against Obesity but Exacerbates Atherosclerosis in Ldlr−/− Mice. Int. J. Mol. Sci. 2018, 19, 510.

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