Adipose Tissue Insulin Action and IL-6 Signaling after Exercise in Obese Mice

• Published in: Medicine and science in sports and exercise Vol. 47; no. 10; p. 2034
• Main Authors: Macpherson, Rebecca E K, Huber, Jason S, Frendo-Cumbo, Scott, Simpson, Jeremy A, Wright, David C
• Format: Journal Article
• Language: English
• Published: United States 01.10.2015
• Subjects: Adipose Tissue - metabolism; Animals; Body Mass Index; Diet, Fat-Restricted; Diet, High-Fat; Insulin - metabolism; Insulin Resistance; Interleukin-10 - metabolism; Interleukin-6 - metabolism; Macrophages - metabolism; Male; MAP Kinase Signaling System - physiology; Mice, Inbred C57BL; Mice, Obese; Physical Conditioning, Animal - physiology; Running - physiology
• ISSN: 1530-0315
• DOI: 10.1249/MSS.0000000000000660

Adipose tissue insulin action is impaired in obesity and is associated with inflammation, macrophage infiltration, and polarization toward a proinflammatory phenotype. Acute exercise can reduce markers of adipose inflammation, including interleukin (IL) 6, in parallel with improvements in insulin action; however, others have provided evidence that IL-6 has anti-inflammatory properties. This study aimed to examine the relation between IL-6 signaling, macrophage infiltration, and polarization and insulin action in inguinal fat after acute exercise in obese, insulin-resistant mice. Male C57BL/6 mice were fed a low-fat diet (10% kcal lard) or a high-fat diet (HFD, 60% kcal lard) for 7 wk and then underwent an acute bout of exercise (2-h treadmill running: 15 m·min, 5% incline). The HFD resulted in increased body mass, glucose intolerance, and attenuated insulin-induced AKT Thr308 phosphorylation in inguinal fat. This was accompanied by increases in indices of macrophage infiltration (F4/80, CD68, and monocyte chemoattractant protein-1 expression) and polarization toward an M1 phenotype (increased expression of CD11c, CD11c/galactose-type C-type lectin 1, and inducible nitric oxide synthase). Immunofluorescence imaging demonstrated increased F4/80- and CD11c-positive cells with the HFD. Two hours after exercise, the insulin-induced activation of AKT Th308 phosphorylation was recovered in HFD mice. This was accompanied by an upregulation of IL-6 and IL-10 signaling, as demonstrated by increased expression of IL-6, IL-10, and SOCS3 as well as STAT3 phosphorylation. Furthermore, acute exercise resulted in a shift toward reduction in M1 polarization indicated by a decrease in the ratio of CD11c to galactose-type C-type lectin 1 mRNA as well as a decline in F4/80- and CD11c-positive cells. The results suggest a link between exercise-induced increases in IL-6, reductions in indices of M1 macrophages, and increased IL-10, a reputed anti-inflammatory cytokine with insulin-sensitizing properties.