Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages

Kizaki, Takako; Maegawa, Taketeru; Sakurai, Takeshi; Ogasawara, Jun; Ookawara, Tomomi; Oh‐ishi, Shuji; Izawa, Tetsuya; Haga, Shukoh; Ohno, Hideki

doi:10.1016/j.bbrc.2011.08.117

Cited by 42 publications

(42 citation statements)

References 28 publications

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“…So, voluntary exercise is ranged in mild / moderate exercise. 14 The aim of this study is to investigate the effect of voluntary exercise on oxidative stress in the heart and blood of diabetic male rats.…”

Section: Introductionmentioning

confidence: 99%

Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats

et al. 2015

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Section: Introductionmentioning

confidence: 99%

Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats

et al. 2015

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“…To evaluate whether obesity influences Rev-erba gene expression in peritoneal macrophages, male 10-wk-old C57BL/6J mice were fed a high-fat diet (HFD) for 6 wk. The diet (HFD60; Oriental Yeast, Tokyo, Japan) consisted of 35% fat by weight and provided 62.2% of its calories from fat (19). Male 2-3-mo-old genetically obese (ob/ob) mice were also used for the experiment.…”

Section: Animalsmentioning

confidence: 99%

A Circadian Clock Gene, Rev-erbα, Modulates the Inflammatory Function of Macrophages through the Negative Regulation of Ccl2 Expression

Sato

Sakurai

Ogasawara

et al. 2014

The Journal of Immunology

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192

169

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Disruption of the circadian rhythm is a contributory factor to clinical and pathophysiological conditions, including cancer, the metabolic syndrome, and inflammation. Chronic and systemic inflammation are a potential trigger of type 2 diabetes and cardiovascular disease and are caused by the infiltration of large numbers of inflammatory macrophages into tissue. Although recent studies identified the circadian clock gene Rev-erbα, a member of the orphan nuclear receptors, as a key mediator between clockwork and inflammation, the molecular mechanism remains unknown. In this study, we demonstrate that Rev-erbα modulates the inflammatory function of macrophages through the direct regulation of Ccl2 expression. Clinical conditions associated with chronic and systemic inflammation, such as aging or obesity, dampened Rev-erbα gene expression in peritoneal macrophages from C57BL/6J mice. Rev-erbα agonists or overexpression of Rev-erbα in the murine macrophage cell line RAW264 suppressed the induction of Ccl2 following an LPS endotoxin challenge. We discovered that Rev-erbα represses Ccl2 expression directly through a Rev-erbα–binding motif in the Ccl2 promoter region. Rev-erbα also suppressed CCL2-activated signals, ERK and p38, which was recovered by the addition of exogenous CCL2. Further, Rev-erbα impaired cell adhesion and migration, which are inflammatory responses activated through the ERK- and p38-signaling pathways, respectively. Peritoneal macrophages from mice lacking Rev-erbα display increases in Ccl2 expression. These data suggest that Rev-erbα regulates the inflammatory infiltration of macrophages through the suppression of Ccl2 expression. Therefore, Rev-erbα may be a key link between aging- or obesity-associated impairment of clockwork and inflammation.

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“…The exercise-induced loss of body mass might be an important factor in the reduction of inflammation. However, it is noteworthy that voluntary exercise almost completely reversed the increases in the expression of these proinflammatory molecules despite the fact that voluntary exercise could not completely reduce fat-body mass in HFD-fed mice 59) . It seems likely, therefore, that exercise training produces some important factors besides loss of body mass in the reduction of low-grade inflammation induced by obesity.…”

Section: Immunosuppressionmentioning

confidence: 99%

The effects of exercise on macrophage function

Kizaki

Sato

Sakurai

et al. 2012

JPFSM

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Innate immunity is our first line of defense against infectious pathogens. One of the major constituents of the innate immune system is macrophages that perform important phagocytic, regulatory and antigen presentation functions. Physically active individuals are reportedly less susceptible than sedentary individuals to viral and bacterial infections, suggesting that exercise improves immune function. Exercise increases the release of catecholamines, glucocorticoids and other factors that have immunomodulatory effects. For example, proinflammatory cytokine production from macrophages was inhibited by β 2 -adrenergic receptor (β 2 AR) agonist catecholamines, but exercise training down-regulated the expression of β 2 AR in macrophages, improving innate immune functions. In addition, the generation of suppressor macrophages by glucocorticoids that are normally induced during acute cold stress was inhibited in swimming-trained mice. Also, an inactive lifestyle leads to the accumulation of visceral fat, which is accompanied by adipose tissue infiltration by pro-inflammatory immune cells, mainly macrophages, and the development of a low-grade systemic inflammatory state. Exercise decreases chronic low-grade systemic inflammation and improves insulin sensitivity in obese individuals. Although the mechanisms behind these favorable effects of exercise are not fully understood, recent studies have shown that exercise training prevents adipose tissue infiltration by pro-inflammatory macrophages and that ghrelin expressed in macrophages functions as a mediator of the anti-inflammatory effects of exercise training. In this Review, the authors focus on the known mechanisms by which exercise exerts its effects on macrophages, and discuss the implications of these effects for the prevention and treatment of disease.

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Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages

Cited by 42 publications

References 28 publications

Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats

Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats

A Circadian Clock Gene, Rev-erbα, Modulates the Inflammatory Function of Macrophages through the Negative Regulation of Ccl2 Expression

The effects of exercise on macrophage function

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