Lack of "immunological fitness" during fasting in metabolically challenged animals

Ingrid Wernstedt Asterholm, John McDonald, Pierre Gilles Blanchard, Madhur Sinha, Qiang Xiao, Jehangir Mistry, Joseph M. Rutkowski, Yves Deshaies, Rolf A. Brekken, Philipp E. Scherer

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Subclinical inflammation is frequently associated with obesity. Here, we aim to better define the acute inflammatory response during fasting. To do so, we analyzed representatives of immune-related proteins in circulation and in tissues as potential markers for adipose tissue inflammation and modulation of the immune system. Lipopolysaccharide treatment or high-fat diet led to an increase in circulating serum amyloid (SAA) and α1-acid glycoprotein (AGP), whereas adipsin levels were reduced. Mouse models that are protected against diet-induced challenges, such as adiponectin-overexpressing animals or mice treated with PPARγ agonists, displayed lower SAA levels and higher adipsin levels. An oral lipid gavage, as well as prolonged fasting, increased circulating SAA concurrent with the elevation of free FA levels. Moreover, prolonged fasting was associated with an increased number of Mac2-positive crown-like structures, an increased capillary permeability, and an increase in several M2-type macrophage markers in adipose tissue. This fasting-induced increase in SAA and M2-type macrophage markers was impaired in metabolically challenged animals. These data suggest that metabolic inflexibility is associated with a lack of "immunological fitness."

Original languageEnglish (US)
Pages (from-to)1254-1267
Number of pages14
JournalJournal of Lipid Research
Volume53
Issue number7
DOIs
Publication statusPublished - Jul 2012

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Keywords

  • Acute phase reactants
  • Adipose tissue
  • Diabetes
  • Inflammation
  • Macrophages
  • Metabolic flexibility
  • Obesity
  • Vascular biology

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Asterholm, I. W., McDonald, J., Blanchard, P. G., Sinha, M., Xiao, Q., Mistry, J., ... Scherer, P. E. (2012). Lack of "immunological fitness" during fasting in metabolically challenged animals. Journal of Lipid Research, 53(7), 1254-1267. https://doi.org/10.1194/jlr.M021725