Deficiency of lymphotoxin-α does not exacerbate high-fat diet-induced obesity but does enhance inflammation in mice.
Lymphotoxin-α (LTα) is secreted by lymphocytes and acts through tumor necrosis factor-α receptors and the LTβ receptor. Our goals were to determine whether LT has a role in obesity and investigate whether LT contributes to the link between obesity and adipose tissue lymphocyte accumulation. LT deficient (LT(-/-)) and wild-type (WT) mice were fed standard pelleted rodent chow or a high-fat/high-sucrose diet (HFHS) for 13 wk. Body weight, body composition, and food intake were measured. Glucose tolerance was assessed. Systemic and adipose tissue inflammatory statuses were evaluated by quantifying plasma adipokine levels and tissue macrophage and T cell-specific gene expression in abdominal fat. LT(-/-) mice were smaller (20%) and leaner (25%) than WT controls after 13 wk of HFHS diet feeding. LT(-/-) mice showed improved glucose tolerance, suggesting that, in WT mice, LT may impair glucose metabolism. Surprisingly, adipose tissue from rodent chow- and HFHS-fed LT(-/-) mice exhibited increased T lymphocyte and macrophage infiltration compared with WT mice. Despite the fact that LT(-/-) mice exhibited an enhanced inflammatory status at the systemic and tissue level even when fed rodent chow, they were protected from enhanced diet-induced obesity and insulin resistance. Thus, LT contributes to body weight and adiposity and is required to modulate the accumulation of immune cells in adipose tissue.
Department of Medicine, Div. of Metabolism, Endocrinology, and Nutrition, Univ. of Washington, Seattle, WA 98109-8050, USA.
Nathalie
N
Pamir
Timothy S
TS
McMillen
Kimberly A
KA
Edgel
Francis
F
Kim
Renée C
RC
LeBoeuf
D054392:Adipokines / Q000097:blood; D052436:Adipose Tissue, White / Q000276:immunology*; D050154:Adiposity; D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D019422:Dietary Sucrose / Q000009:adverse effects; D015870:Gene Expression; D005786:Gene Expression Regulation; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D007333:Insulin Resistance; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015430:Weight Gain
D054392:Adipokines; D016207:Cytokines; D019422:Dietary Sucrose; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger