title: Lack of "immunological fitness" during fasting in metabolically challenged animals.
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 adip-sin 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."
authors.affiliation: Touchstone Diabetes Center, Departments of Internal Medicine, University of Texas Southwestern Medical Center , Dallas, TX 75390, USA.
authors.forename: Ingrid Wernstedt
authors.initials: IW
authors.lastname: Asterholm
authors.forename: John
authors.initials: J
authors.lastname: McDonald
authors.forename: Pierre-Gilles
authors.initials: PG
authors.lastname: Blanchard
authors.forename: Madhur
authors.initials: M
authors.lastname: Sinha
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xiao
authors.forename: Jehangir
authors.initials: J
authors.lastname: Mistry
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Rutkowski
authors.forename: Yves
authors.initials: Y
authors.lastname: Deshaies
authors.forename: Rolf A
authors.initials: RA
authors.lastname: Brekken
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
mesh_terms: D000682:Amyloid / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D005215:Fasting / Q000378:metabolism* / Q000502:physiology; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009961:Orosomucoid / Q000032:analysis
chemical_list: D000682:Amyloid; D015415:Biomarkers; D008070:Lipopolysaccharides; D009961:Orosomucoid