Exercise Attenuates M1 Macrophages and CD8+ T Cells in the Adipose Tissue of Obese Mice

Kawanishi, Noriaki; Mizokami, Tsubasa; Yano, Hiromi

doi:10.1249/mss.0b013e31828ff9c6

Cited by 117 publications

(101 citation statements)

References 32 publications

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“…Existing evidence in animals and humans indicates that exercise results in reduced expression of inflammatory genes and markers of immune cell infiltration in white AT (9,18,28,30,60,61). We found that voluntary WR-induced decreases in adiposity produced, by and large, similar downregulation of inflammatory genes in white AT (retroperitoneal) to that produced by decreases in adiposity with 30% DR regimen.…”

Section: Discussionsupporting

confidence: 51%

“…Overall, our data indicate that the greatest effects of WR and DR on AT gene expression were in visceral AT. While visceral AT is highly susceptible to obesity-mediated inflammation/infiltration of immune cells (18,28,30,60,61), these data suggest that the phenotype of visceral AT is also highly amenable to reductions in adiposity. Given this close link between visceral AT expansion and inflammation in obesity (18,28,30,60,61), it is not surprising that measures of central adiposity in humans relate with metabolic and cardiovascular outcomes (21) and that interventions that result in weight loss are associated with improvements in insulin sensitivity and cardiovascular health (22).…”

Section: Discussionmentioning

confidence: 87%

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Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

Crissey

Jenkins

Lansford

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Adipose tissue (AT)-derived cytokines are proposed to contribute to obesity-associated vascular insulin resistance. We tested the hypothesis that voluntary physical activity and diet restriction-induced maintenance of body weight would both result in decreased AT inflammation and concomitant improvements in insulin-stimulated vascular relaxation in the hyperphagic, obese Otsuka Long-Evans Tokushima fatty (OLETF) rat. Rats (aged 12 wk) were randomly assigned to sedentary (SED; n ϭ 10), wheel running (WR; n ϭ 10), or diet restriction (DR; n ϭ 10; fed 70% of SED) for 8 wk. WR and DR rats exhibited markedly lower adiposity (7.1 Ϯ 0.4 and 15.7 Ϯ 1.1% body fat, respectively) relative to SED (27 Ϯ 1.2% body fat), as well as improved blood lipid profiles and systemic markers of insulin resistance. Reduced adiposity in both WR and DR was associated with decreased AT mRNA expression of inflammatory genes (e.g., MCP-1, TNF-␣, and IL-6) and markers of immune cell infiltration (e.g., CD8, CD11c, and F4/80). The extent of these effects were most pronounced in visceral AT compared with subcutaneous and periaortic AT. Markers of inflammation in brown AT were upregulated with WR but not DR. In periaortic AT, WR-and DR-induced reductions in expression and secretion of cytokines were accompanied with a more atheroprotective gene expression profile in the adjacent aortic wall. WR, but not DR, resulted in greater insulin-stimulated relaxation in the aorta; an effect that was, in part, mediated by a decrease in insulin-induced endothelin-1 activation in WR aorta. Collectively, we show in OLETF rats that lower adiposity leads to less AT and aortic inflammation, as well as an exercise-specific improvement in insulin-stimulated vasorelaxation. calorie restriction; exercise; gene expression; inflammation; obesity MORE THAN ONE-THIRD OF AMERICANS are obese (38), and the causes underlying the obesity epidemic appear to be largely related to physical inactivity and overnutrition, a set of behaviors increasingly prevalent in our society (5-7, 11, 57). Cumulative evidence indicates that obesity is an important contributor to the development of whole body insulin resistance, Type 2 diabetes, and cardiovascular disease (21). A critical link between obesity and its associated metabolic and cardiovascular diseases is thought to be chronic low-grade systemic inflammation (21). In this regard, recent studies implicate adipose tissue (AT) as a local and systemic source of inflammatory cytokines that may be involved in the instigation of vascular insulin resistance and atherosclerosis associated with obesity (12, 13, 19, 20, 31, 33-36, 45, 46, 51, 55, 56). Indeed, excessive lipid accumulation and enlargement of adipocytes in obesity are associated with infiltration of immune cells into AT, contributing to AT inflammation and subsequent secretion of proinflammatory cytokines (52). A deeper understanding of the influence of lifestyle modifications on AT inflammation and vascular insulin resistance may lead to more effective strategies aimed at prevent...

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 87%

Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

Crissey

Jenkins

Lansford

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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show abstract

“…However, studies in less overweight individuals have shown similar results [66]. Exercise also significantly reduced circulating levels of LPS and TLR4 activation, lowered M1 macrophage infiltration, and improved insulin sensitivity in mice fed a high-fat diet [67,68]. The temporal response to caloric restriction in diet-induced obese mice was recently examined [32].…”

Section: Diet and Lifestyle Interventionsmentioning

confidence: 95%

Do adipose tissue macrophages promote insulin resistance or adipose tissue remodelling in humans?

Heilbronn¹,

Liu²

2014

Hormone Molecular Biology and Clinical Investigation

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In diet induced and genetically obese rodent models, adipose tissue is associated with macrophage infiltration, which promotes a low grade inflammatory state and the development of insulin resistance. In humans, obesity is also closely linked with macrophage infiltration in adipose tissue, a pro-inflammatory phenotype and insulin resistance. However, whether macrophage infiltration is a direct contributor to the development of insulin resistance that occurs in response to weight gain, or is a later consequence of the obese state is unclear. There are a number of concomitant changes that occur during adipose tissue expansion, including the number and size of adipocytes, the vasculature and the extracellular matrix. In this review, we will examine evidence for and against the role of macrophage recruitment into adipose tissue in promoting the development of insulin resistance in rodents and humans, as well as discuss the emerging role of macrophages in mediating healthy adipose tissue expansion during periods of caloric excess.

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“…We also analyzed the characteristics of the macrophages in epididymal visceral AT by flow cytometry and found that exercise training not only decreased the cell number of macrophages, but also changed the ratio of the macrophage subsets in the AT of obese mice (Kawanishi et al. 2013). These results indicate that chronic endurance exercise may improve AT inflammation by changing the number and subset composition of macrophages.…”

Section: Introductionmentioning

confidence: 99%

Exercise training attenuates neutrophil infiltration and elastase expression in adipose tissue of high-fat-diet-induced obese mice

et al. 2015

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The innate immune system is associated with the development of local inflammation. Neutrophils play an essential role in the development of the adipose tissue (AT) inflammation associated with obesity by producing elastase, which can promote the activation and infiltration of macrophages. Exercise training attenuates AT inflammation via suppression of macrophage infiltration. However, the mechanisms driving this phenomenon remains to be elucidated. Here, we evaluated the effects of exercise training on the infiltration of neutrophils and elastase expression in an obese mouse model. Four-week-old male C57BL/6J mice were randomly assigned to one of three groups that either received a normal diet (ND) plus sedentary activity (n = 15), a high-fat diet (HFD) plus sedentary activity (n = 15), or a HFD plus exercise training (n = 15). Mice were fed the ND or HFD from the age of 4 weeks until 20 weeks. Mice in the exercise group ran on a treadmill for 60 min/day, 5 days/week over the same experimental period. Mice fed with the HFD had increased content of macrophages in the AT and increased inflammatory cytokine mRNA levels, which were reduced by exercise training. Similarly, AT from the HFD sedentary mice contained more neutrophils than AT from the ND mice, and the amount of neutrophils in this tissue in HFD-fed mice was lowered by exercise training. The mRNA levels of neutrophil elastase in AT were lower in the HFD exercise-trained mice than those in the HFD sedentary mice. These results suggest that exercise training plays a critical role in reducing macrophage infiltration and AT inflammation by regulating the infiltration of neutrophils.

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Exercise Attenuates M1 Macrophages and CD8+ T Cells in the Adipose Tissue of Obese Mice

Abstract: The results suggest that exercise training reduces adipose tissue inflammation by suppressing infiltration of inflammatory macrophages and CD8 T cells.

Cited by 117 publications

References 32 publications

Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

Do adipose tissue macrophages promote insulin resistance or adipose tissue remodelling in humans?

Exercise training attenuates neutrophil infiltration and elastase expression in adipose tissue of high-fat-diet-induced obese mice

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