Inflammation and adipose tissue macrophages in lipodystrophic mice

Laura Herrero, Hagit Shapiro, Ali Nayer, Jongsoon Lee, Steven E. Shoelson

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Lipodystrophy and obesity are opposites in terms of a deficiency versus excess of adipose tissue mass, yet these conditions are accompanied by similar metabolic consequences, including insulin resistance, dyslipidemia, hepatic steatosis, and increased risk for diabetes and atherosclerosis. Hepatic and myocellular steatosis likely contribute to metabolic dysregulation in both states. Inflammation and macrophage infiltration into adipose tissue also appear to participate in the pathogenesis of obesity-induced insulin resistance, but their contributions to lipodystrophy-induced insulin resistance have not been evaluated. We used aP2-nSREBP-1c transgenic (Tg) mice, an established model of lipodystrophy, to ask this question. Circulating cytokine elevations suggested systemic inflammation but even more dramatic was the number of infiltrating macrophages in all white and brown adipose tissue depots of the Tg mice; in contrast, there was no evidence of inflammatory infiltrates or responses in any other tissue including liver. Despite there being overt evidence of adipose tissue inflammation, antiinflammatory strategies including salicylate treatment and genetic suppression of myeloid NF-κB signaling that correct insulin resistance in obesity were ineffective in the lipodystrophic mice. We further showed that adipose tissue macrophages (ATMs) in lipodystrophy and obesity are very different in terms of activation state, gene expression patterns, and response to lipopolysaccharide. Although ATMs are even more abundant in lipodystrophy than in obesity, they have distinct phenotypes and likely roles in tissue remodeling, but do not appear to be involved in the pathogenesis of insulin resistance.

Original languageEnglish (US)
Pages (from-to)240-245
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number1
DOIs
StatePublished - 2010

Keywords

  • Diabetes
  • Insulin resistance
  • Obesity

ASJC Scopus subject areas

  • General

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