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."
- SourceAvailable from: Risheng Ye
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- "High molecular weight (HMW, 18–36 multimers) adiponectin is generally more abundant in females, in both proportion and absolute amounts, while males lean more towards trimers or hexamers   . Only two adipocyte-derived factors display levels with an inverse correlation with fat mass, one is adipsin (complement factor D) the other one is adiponectin . Adiponectin shows a marked reduction of its circulating levels and secretion rate in humans with obesity and insulin resistance  . "
ABSTRACT: Almost 20 years have passed since the first laboratory evidence emerged that an abundant message encoding a protein with homology to the C1q superfamily is highly specifically expressed in adipocytes. At this stage, we refer to this protein as adiponectin. Despite more than 10,000 reports in the literature since its initial description, we seem to have written only the first chapter in the textbook on adiponectin physiology. With every new aspect we learn about adiponectin, a host of new questions arise with respect to the underlying molecular mechanisms. Here, we aim to summarize recent findings in the field and bring the rodent studies that suggest a causal relationship between adiponectin levels in plasma and systemic insulin sensitivity in perspective with the currently available data on the clinical side.Molecular Metabolism 08/2013; 2(3):133-141. DOI:10.1016/j.molmet.2013.04.001
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ABSTRACT: Adipose tissue remodeling is a dynamic process during nutritional fluctuation that plays critical roles in metabolic homeostasis and insulin sensitivity. The process is highly regulated by many factors, including adipokines and cytokines that are locally released within fat pads. In a recent study published in Nature, Jonker and colleagues identified FGF1 as an important mediator that is selectively induced in fat cells by high-fat diet feeding and established the PPARγ-FGF1 axis as a critical pathway that regulates adipose tissue remodeling and ultimately systemic metabolic homeostasis.Cell Research 06/2012; 22(10):1416-8. DOI:10.1038/cr.2012.94 · 12.41 Impact Factor
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ABSTRACT: Inflammation induced by wound healing or infection activates local vascular endothelial cells to mediate leukocyte rolling, adhesion, and extravasation by upregulation of leukocyte adhesion molecules such as E-selectin and P-selectin. Obesity-associated adipose tissue inflammation has been suggested to cause insulin resistance, but weight loss and lipolysis also promote adipose tissue immune responses. While leukocyte-endothelial interactions are required for obesity-induced inflammation of adipose tissue, it is not known whether lipolysisinduced inflammation requires activation of endothelial cells. Here, we show that β3- adrenergic receptor stimulation by CL 316,243 promotes adipose tissue neutrophil infiltration in wild type and P-selectin null mice but not in E-selectin null mice. Increased expression of adipose tissue cytokines IL-1β, CCL2, and TNF-α in response to CL 316,243 administration is also dependent upon Eselectin but not P-selectin. In contrast, fasting increases adipose-resident macrophages but not neutrophils, and does not activate adiposeresident endothelium. Thus, two models of lipolysis-induced inflammation induce distinct immune cell populations within adipose tissue and exhibit distinct dependencies on endothelial activation. Importantly, our results indicate that β3-adrenergic stimulation acts through upregulation of E-selectin in adipose tissue endothelial cells to induce neutrophil infiltration.Journal of Biological Chemistry 12/2012; 288(4). DOI:10.1074/jbc.M112.412346 · 4.57 Impact Factor