Deficiency of lymphotoxin-a does not exacerbate high-fat diet-induced obesity but does enhance inflammation in mice

Nathalie Pamir, Timothy S. McMillen, Kimberly A. Edgel, Francis Kim, Renée C. Leboeuf

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Lymphotoxin-α (LT-α) is secreted by lymphocytes and acts through tumor necrosis factor-a 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.

Original languageEnglish (US)
Pages (from-to)E961-E971
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume302
Issue number8
DOIs
StatePublished - Apr 15 2012

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Keywords

  • Cytokines
  • Diabetes
  • Lymphocytes
  • Macrophages

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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