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

Abstract

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.

Impact of physical exercise on visceral adipose tissue fatty acid profile and inflammation in response to a high-fat diet regimen

“…Our findings are in line with these data as higher levels of plasma TNF-α and MCP-1, one of the key chemokines that regulate the monocytes/macrophage migration and infiltration, were found in sedentary HFD-fed animals. On the other hand, ET was effective as a therapeutic intervention and reverted the moderate pro-inflammatory phenotype imposed by the HFD, which is consistent with the well-described anti-inflammatory effects of exercise (5,17,26,49).…”

“…In humans, the most abundant FA esterified to triglycerides are oleic (C18:1n9), palmitic (C16:0) and linoleic (C18:2n6) that account for over 85% of FA in WAT triglycerides (3). Some FA have been suggested to be involved as direct regulators in inflammation (1, 2), a complex and tightly regulated biological process that is triggered by obesity (4,5). Obesity is the result of a positive energy intake with low levels of physical activity, interacting or not with genetic factors, which explain at least in part the excess of visceral adiposity accumulation observed in large proportions worldwide (6).…”

“…Physical exercise has been well recognized as a strategy to prevent visceral adiposity accumulation, improve inflammatory process as well as lipid metabolism, such as fatty acid profile (4,5,17,18). In fact, studies demonstrated that endurance training (ET) induced FA profile-specific changes in WAT triglycerides by increasing the percentage of long chain and PUFA (19-21).…”

“…Moreover, ET decreased MUFA in humans (22, 23) and in rodents (20, 24); however the findings are not consistent (21, 25). The antiinflammatory impact of regular physical exercise are well documented (5,17,18) and rely on several modulatory effects, such as decreased expression of pro-inflammatory cytokines (TNF-α and IL-6) and macrophage recruitment and infiltration (17, 26) independently of body weight reduction (4). In addition, an increased IL-10 expression was also observed in response to ET (18, 27, 28), strengthening the anti-inflammatory effects of physical exercise.…”

NAFLD Preclinical Models: More than a Handful, Less of a Concern?

“…In this study, mice were either challenged with voluntary wheel running or were kept on a sedentary lifestyle intervention [125]. Similar to well-known forced exercise models [126], voluntary wheel running protected these mice from HFD-induced pro-inflammatory and pro-fibrogenic states, as shown by decreased hepatic macrophage infiltration and improved fatty acid and glucose homeostasis. These data were in line with Kawanishi et al [126], showing that exercise training reduced macrophage infiltration and adipose tissue inflammation by attenuating neutrophil infiltration in HFD-fed C57BL/6 mice.…”