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

MacPherson, Rebecca E. K.; Huber, Jason S.; Frendo‐Cumbo, Scott; Simpson, Jeremy A.; Wright, David C.

doi:10.1249/mss.0000000000000660

Cited by 53 publications

(53 citation statements)

References 39 publications

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“…Oliveira et al (2013) found that acute swim exercise led to reductions in markers of M1, pro-inflammatory macrophages, and increases in anti-inflammatory M2 macrophages in adipose tissue from rats fed a high-fat diet. Consistent with these findings, MacPherson et al (2015) reported reductions in indices of M1 macrophages, via quantitative polymerase chain reaction and immunofluorescence, in inguinal subcutaneous adipose tissue from mice fed a high-fat diet following a single bout of treadmill running.…”

Section: Does Acute Exercise Reduce Inflammation and Improve Glucose supporting

confidence: 61%

“…In support of this, IL-6 mRNA expression and markers of IL-6 signaling such as SOCS3 (suppressor of cytokine signaling 3) mRNA and signal transducer and activator of transcription 3 phosphorylation are increased in parallel with reductions in M1 macrophages and increases in insulin-stimulated Akt phosphorylation in inguinal adipose tissue from obese mice (MacPherson et al 2015). In contrast to higher intensity exercise in lean, healthy animals, the induction of IL-6 signaling with exercise in adipose tissue from obese mice occurs independent of increases in classically identified markers of inflammation such as TNFα and c-Jun N-terminal kinase phosphorylation.…”

Section: Is There a Common Mechanism That Explains The Protective Effmentioning

confidence: 92%

“…While forced swim exercise is stressful and has little clinical significance, similar results have been reported with treadmill exercise. MacPherson et al (2015) reported that a single bout of treadmill running almost completely rescued high-fat diet–induced insulin resistance in inguinal subcutaneous mouse adipose tissue. Rapid improvements in adipose tissue insulin action with exercise are associated with a shift in macrophage polarization.…”

Section: Does Acute Exercise Reduce Inflammation and Improve Glucose mentioning

confidence: 99%

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“Weighing” the effects of exercise and intrinsic aerobic capacity: are there beneficial effects independent of changes in weight?

Thyfault

Wright

2016

Appl. Physiol. Nutr. Metab.

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It has been known for centuries that regularly performed exercise has beneficial effects on metabolic health. Owing to its central role in locomotion and the fact that it accounts for a large majority of whole-body glucose disposal and fatty acid oxidation, the effects of exercise on skeletal muscle has been a central focus in exercise physiology research. With this being said it is becoming increasingly well recognized that both adipose tissue and liver metabolism are robustly modified by exercise, especially in conditions of obesity and insulin resistance. One of the difficult questions to address is if the effects of exercise are direct or occur secondary to exercise-induced weight loss. The purpose of this review is to highlight recent work that has attempted to tease out the protective effects of exercise, or intrinsic aerobic capacity, against metabolic and inflammatory challenges as it relates to the treatment and prevention of obesity and insulin resistance. Recent studies reporting improvements in liver and adipose tissue insulin action following a single bout of exercise will also be discussed. The research highlighted in this review sheds new insight into protective, anti-inflammatory effects of exercise that occur largely independent of changes in adiposity and body weight.

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Section: Does Acute Exercise Reduce Inflammation and Improve Glucose supporting

confidence: 61%

Section: Is There a Common Mechanism That Explains The Protective Effmentioning

confidence: 92%

Section: Does Acute Exercise Reduce Inflammation and Improve Glucose mentioning

confidence: 99%

See 1 more Smart Citation

“Weighing” the effects of exercise and intrinsic aerobic capacity: are there beneficial effects independent of changes in weight?

Thyfault

Wright

2016

Appl. Physiol. Nutr. Metab.

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“…Exercise is an emerging pro-myelination therapeutic intervention for many pathologies including demyelinating disease (Sampaio-Baptista et al, 2013;Scholz et al, 2009) and is associated with elevated BDNF levels and increased neuronal activity (Gold et al, 2003). Exercise can shift macrophage polarization from an M1 to an M2 state (Goh and Ladiges, 2014;Macpherson et al, 2015) and be used as a preemptive strategy to mitigate demyelinating disease (Bernardes et al, 2016). Whether it has an identical molecular signature and impact as direct nerve stimulation remains to be determined, but is promising as a non-interventional adjunct therapy.…”

Section: Potential Mechanisms Regulating Macrophage Switch From M1 Tomentioning

confidence: 99%

Dynamic impact of brief electrical nerve stimulation on the neural immune axis—polarization of macrophages toward a pro‐repair phenotype in demyelinated peripheral nerve

McLean

Verge

2016

Glia

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Demyelinating peripheral nerves are infiltrated by cells of the monocyte lineage, including macrophages, which are highly plastic, existing on a continuum from pro-inflammatory M1 to pro-repair M2 phenotypic states. Whether one can therapeutically manipulate demyelinated peripheral nerves to promote a pro-repair M2 phenotype remains to be elucidated. We previously identified brief electrical nerve stimulation (ES) as therapeutically beneficial for remyelination, benefits which include accelerated clearance of macrophages, making us theorize that ES alters the local immune response. Thus, the impact of ES on the immune microenvironment in the zone of demyelination was examined. Adult male rat tibial nerves were focally demyelinated via 1% lysophosphatidyl choline (LPC) injection. Five days later, half underwent 1 hour 20 Hz sciatic nerve ES proximal to the LPC injection site. ES had a remarkable and significant impact, shifting the macrophage phenotype from predominantly pro-inflammatory/M1 toward a predominantly pro-repair/M2 one, as evidenced by an increased incidence of expression of M2-associated phenotypic markers in identified macrophages and a decrease in M1-associated marker expression. This was discernible at 3 days post-ES (8 days post-LPC) and continued at the 5 day post-ES (10 days post-LPC) time point examined. ES also affected chemokine (C-C motif) ligand 2 (CCL2; aka MCP-1) expression in a manner that correlated with increases and decreases in macrophage numbers observed in the demyelination zone. The data establish that briefly increasing neuronal activity favorably alters the immune microenvironment in demyelinated nerve, rapidly polarizing macrophages toward a pro-repair phenotype, a beneficial therapeutic concept that may extend to other pathologies. GLIA 2016;64:1546-1561.

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“…Approximately 100 mg of eWAT and scAT were fixed in 10% neutral-buffered formalin (VWR, Mississauga, ON, Canada), dehydrated in 70% ethanol (Fisher Scientific), and embedded in paraffin. Five micrometer sections were mounted on 1.2 mm Superfrost slides, stained with Harris hematoxylin and eosin stock (H&E; Fisher Scientific) and imaged (Olympus FSX 100 light microscope, Olympus, Tokyo, Japan) as previously described (MacPherson et al 2015). Cells were sampled in each image to determine cross-sectional area (>200 cells/mouse) (ImageJ software, National Institute of Mental Health, Bethesda, MD).…”

Section: Histologymentioning

confidence: 99%

Beneficial effects of combined resveratrol and metformin therapy in treating diet‐induced insulin resistance

Frendo‐Cumbo

MacPherson

Wright

2016

Physiological Reports

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The polyphenol compound resveratrol (RSV) has attracted attention due to its reputed beneficial effects on insulin sensitivity. Our lab has previously identified protective effects of RSV against the development of type 2 diabetes in rats. These effects occurred in a manner similar to thiazolidinedione's (TZDs), a class of insulin sensitizing drugs. TZDs are commonly prescribed in combination with metformin (MET) and thus we sought to examine the combined effects of RSV and MET in treating insulin resistance. Male C57BL6 mice were fed a low‐ (LFD; 10% Kcal from fat) or high‐fat diet (HFD; 60% Kcal from fat) for 9 weeks to induce glucose and insulin intolerance. HFD mice were then assigned to control (HFD), MET (231.28 ± 12.24 mg/kg/day), RSV (93.68 ± 3.51 mg/kg/day), or combined (COM; MET 232.01 ± 17.12 mg/kg/day and RSV 92.77 ± 6.92 mg/kg/day) treatment groups. Changes in glucose and insulin tolerance and tissue‐specific insulin signaling were measured 4 weeks post‐treatment. RSV or MET alone did not have beneficial effects on glucose tolerance, although MET significantly improved insulin tolerance compared to HFD. Glucose and insulin tolerance were significantly improved in COM compared to HFD and this was mirrored by enhanced insulin‐stimulated AKT phosphorylation in triceps muscle and inguinal subcutaneous adipose tissue in COM compared to HFD mice. Improvements with COM treatment were not explained by differences in body weight, adiposity, or markers of adipose tissue inflammation. In summary, this study provides evidence of beneficial effects of combined RSV and MET therapy in treating impairments in glucose homeostasis.

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

Abstract: 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.

Cited by 53 publications

References 39 publications

“Weighing” the effects of exercise and intrinsic aerobic capacity: are there beneficial effects independent of changes in weight?

“Weighing” the effects of exercise and intrinsic aerobic capacity: are there beneficial effects independent of changes in weight?

Dynamic impact of brief electrical nerve stimulation on the neural immune axis—polarization of macrophages toward a pro‐repair phenotype in demyelinated peripheral nerve

Beneficial effects of combined resveratrol and metformin therapy in treating diet‐induced insulin resistance

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