Inflammation and adipose tissue macrophages in lipodystrophic mice

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

Research output: Contribution to journalArticle

93 Citations (Scopus)

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
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 - Feb 15 2010
Externally publishedYes

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Lipodystrophy
Insulin Resistance
Adipose Tissue
Obesity
Macrophages
Inflammation
Transgenic Mice
Liver
Genetic Suppression
White Adipose Tissue
Brown Adipose Tissue
Salicylates
Dyslipidemias
Lipopolysaccharides
Atherosclerosis
Anti-Inflammatory Agents
Cytokines
Phenotype
Gene Expression

Keywords

  • Diabetes
  • Insulin resistance
  • Obesity

ASJC Scopus subject areas

  • General

Cite this

Inflammation and adipose tissue macrophages in lipodystrophic mice. / Herrero, Laura; Shapiro, Hagit; Nayer, Ali; Lee, Jongsoon; Shoelson, Steven E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 1, 15.02.2010, p. 240-245.

Research output: Contribution to journalArticle

Herrero, Laura ; Shapiro, Hagit ; Nayer, Ali ; Lee, Jongsoon ; Shoelson, Steven E. / Inflammation and adipose tissue macrophages in lipodystrophic mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 1. pp. 240-245.
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