Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 33, Issue 6, Pages 1189-+Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.112.301105
Keywords
immune system; leukocytes; lipases; NKT cells; obesity
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Funding
- Swedish Research Council [521-2009-4203, 349-2007-8703]
- Swedish Heart-Lung Foundation
- Foundation for Strategic Research
- Vinnova Foundation
- Stockholm County Council
- European Commission (AtheroRemo collaborative project)
- Loo and Hans Ostermans foundation
- Strategic Research Program in Diabetes at Karolinska Institute
- Leducq Network on Atherothrombosis
- Novo Nordisk Fonden [NNF12OC1016371] Funding Source: researchfish
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Objective-Obesity promotes a chronic inflammatory condition in adipose tissue (AT). Impairment of insulin sensitivity coincides with infiltration of T cells into AT in early stages of obesity, when macrophages are not yet present. Here, we examine the role of invariant natural killer T (iNKT) cells, a subtype of T cells activated by lipid antigens, on glucose and lipid metabolism in obesity. Approach and Results-J alpha 18(-/-) mice, specifically lacking iNKT cells, and wild-type mice consumed a chow or high-fat diet for 10 weeks. One third of all T lymphocytes in the liver of wild-type mice were iNKT cells, whereas few were detected in AT. Diet-induced obesity increased blood glucose in both genotypes of mice, whereas glucose tolerance test revealed similar kinetics of glucose clearance in J alpha 18(-/-) and wild-type mice. Under obese conditions, expression of inflammatory cytokines in AT did not differ between the groups, although the number of T cells and macrophages was lower in J alpha 18(-/-) mice. Nonetheless, AT homeostasis in J alpha 18(-/-) mice was altered evidenced by lower AT weight, smaller adipocytes, accelerated lipogenesis, increased expression of hormone-sensitive lipase, and accelerated basal lipolysis. Conclusions-iNKT cells do not affect glucose clearance but rather modulate lipid metabolism in both liver and AT. Only few iNKT cells are found in AT under lean and obese conditions, suggesting that their effects on lipid metabolism are mainly mediated in the liver, their primary host organ.
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