Exercise improves adipose function and inflammation and ameliorates fatty liver disease in obese diabetic mice

Haczeyni, Fahrettin; Barn, Vanessa; Mridha, Auvro R.; Yeh, Matthew M.; Estévez, Emma; Febbraio, Mark A.; Nolan, Christopher; Bell-Anderson, Kim; Teoh, Narci C.; Farrell, Geoffrey C.

doi:10.1002/oby.21170

Cited by 44 publications

(52 citation statements)

References 39 publications

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“…15 As these effects occur in parallel with a reduction in adiposity, it is likely that at least a portion of the reductions in inflammatory markers are secondary to alterations in adipose tissue accretion. 15,17 In this regard, a recent study from Welly and colleagues demonstrated that caloric restriction as a means to match the reduction in adiposity induced by VWR, led to similar effects on inflammatory gene expression when rats were fed a high fat diet. 16 The results from our current study support and add to these previous studies, as we observed that VWR attenuated the LPSmediated induction of TNF-a and MCP-1 mRNA expression in iWAT providing some evidence that the effects of VWR go beyond the attenuation of weight gain.…”

Section: Discussionmentioning

confidence: 99%

“…Physical activity and exercise training increase indices of mitochondrial biogenesis in adipose tissue [9][10][11][12] and induce a thermogenic gene program that is characterized by increases in uncoupling protein 1 (UCP-1) mRNA expression and/or protein content in some 9,13,14 but not all studies. 15,16 While physical activity can protect against adipose tissue inflammation induced by obesity, 15,17 this beneficial anti-inflammatory effect is likely mediated, at least in part, through reducing the accretion of adipose tissue. 18 Thus, as the inflammatory cascade induced by sepsis manifests without significant changes in the accretion of adipose tissue, it is important to determine if physical activity or exercise protect against sepsis induced inflammation in adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

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Habitual physical activity protects against lipopolysaccharide-induced inflammation in mouse adipose tissue

et al. 2016

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Sepsis is a systemic inflammatory response to infection, with no preventative strategies. In this study, we identify a role for habitual physical activity in the prevention of adipose tissue inflammation induced by a model of sepsis, lipopolysaccharide (LPS). Male C57BL/6J mice (8 weeks old) were housed with access to voluntary wheel running (VWR) or sedentary (SED) for 10 weeks. Mice were then injected with LPS (2 mg/kg) or saline (SAL), and tissues were removed 6 hours postinjection. VWR attenuated body, epididymal adipose tissue (eWAT), and subcutaneous inguinal adipose tissue (iWAT) mass gain, improved glucose tolerance, increased markers of mitochondrial biogenesis in iWAT and eWAT, and increased UCP-1 protein content in iWAT. In iWAT, VWR attenuated the LPS induced increase in mRNA expression of TNF-a, MCP-1, and follistatin, along with phosphorylation of STAT3. In addition, VWR had a main effect for reducing iWAT mRNA expression of IL-1b, IL-6, and SOCS3. In eWAT, VWR had a main effect for reducing mRNA expression of IL-1b, MCP-1, IL-6, and follistatin. Further, VWR increased SOCS3 mRNA expression and phosphorylation of STAT3 in SAL mice, thus the relative change in response to LPS for these markers was attenuated. The protective effect of prior physical activity occurred in conjunction with increases in the protein content of a component of the LPS binding complex, MyD88. Overall, the results from this study demonstrate that habitual physical activity can attenuate the LPS induced inflammatory response in adipose tissue and this occurs to a greater extent in iWAT compare with eWAT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Habitual physical activity protects against lipopolysaccharide-induced inflammation in mouse adipose tissue

et al. 2016

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“…Exercise is a key modulator of cardiometabolic health [121] and elicits a number of benefits on adipose tissues including a reduction in cell number/size and inflammation [122], upregulated angiogenesis [123] and mitochondrial biogenesis [124]. In recent years it has emerged that another mechanism by which exercise improves metabolic health in rodents is by the browning of WAT whereby myokines, produced during muscular contractions, are secreted into the circulation and act in an endocrine manner on adipose tissues [125], [126].…”

Section: ‘Browning’ Cardiac and Vascular Adipose Tissues To Reduce Camentioning

confidence: 99%

‘Browning’ the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk

Aldiss

Davies

Woods

et al. 2017

International Journal of Cardiology

113

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Excess visceral adiposity, in particular that located adjacent to the heart and coronary arteries is associated with increased cardiovascular risk. In the pathophysiological state, dysfunctional adipose tissue secretes an array of factors modulating vascular function and driving atherogenesis. Conversely, brown and beige adipose tissues utilise glucose and lipids to generate heat and are associated with improved cardiometabolic health. The cardiac and thoracic perivascular adipose tissues are now understood to be composed of brown adipose tissue in the healthy state and undergo a brown-to-white transition i.e. during obesity which may be a driving factor of cardiovascular disease. In this review we discuss the risks of excess cardiac and vascular adiposity and potential mechanisms by which restoring the brown phenotype i.e. “re-browning” could potentially be achieved in clinically relevant populations.

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“…12 Animal models support these clinical findings. Voluntary wheel running was shown to decrease inflammation in adipose tissue and decrease the severity of NASH and hepatic fibrosis in both a genetic foz/foz 13 and a dietary high-fat model 14 of NASH.…”

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confidence: 99%

Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu

et al. 2017

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Physical activity confers a broad spectrum of health benefits. Beyond the obvious role in metabolically driven diseases, the role of physical activity in acute liver injury is poorly explored. To study the role of physical activity in acute liver injury, a novel model of voluntary distance running in mice was developed and mice were subjected to acute liver injury induced by N-galactosamine (GalN) and lipopolysaccharide (LPS). Analyses included histological stains, immunoblotting, qRT-PCR and FACS analysis. Voluntary distance running increased to an average of 10.3 km/day after a learning curve. Running lead to a decrease in the absolute numbers of intrahepatic CD4+ T and B lymphocytes and macrophages after 7 weeks. In parallel, hepatic mRNA expression of inflammatory cytokines including IL-6 and IL-1beta, TGF-beta and monocyte chemoattractant protein-1 (MCP-1/CCL2) were suppressed, while TNF-α was not affected by exercise. Likewise, expression of the macrophage-specific antigen F4/80 was downregulated 1.6-fold from exercise. Notably, acute liver injury from GaIN/LPS was significantly blunted following 7 weeks of voluntary exercise as determined by liver histology, a 84.6% reduction of alanine aminotransferase (P<0.01) and a 54.6% reduction of aspartate aminotransferase (P<0.05) compared with sedentary mice. Additionally, proinflammatory cytokines, activation of caspase 3 and JNK were significantly lower, while antiapoptotic protein A20 increased. Voluntary distance running alters the intrahepatic immune phenotype producing an environment that is less susceptible to acute liver injury.

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Exercise improves adipose function and inflammation and ameliorates fatty liver disease in obese diabetic mice

Abstract: Exercise confers metabo-protective effects in atherogenic-fed hyperphagic mice by preventing early onset of obesity and diabetes in association with enhanced muscle insulin sensitivity, improved adipose morphometry, and suppressed adipose and liver inflammation.

Cited by 44 publications

References 39 publications

Habitual physical activity protects against lipopolysaccharide-induced inflammation in mouse adipose tissue

Habitual physical activity protects against lipopolysaccharide-induced inflammation in mouse adipose tissue

‘Browning’ the cardiac and peri-vascular adipose tissues to modulate cardiovascular risk

Voluntary distance running prevents TNF-mediated liver injury in mice through alterations of the intrahepatic immune milieu

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