Abstract
Obesity is a chronic low-grade inflammatory condition, and β2-adrenergic agonists as well as exercise have been proposed as anti-inflammatory strategies in obesity, so it is critical to accurately determine the effects of β2-adrenergic stimulation, especially when combined with other non-pharmacological therapies. The aim of this investigation was to determine the effect of β2-adrenergic activation on the inflammatory profile and phenotype of macrophages, and whether these effects could be affected by obesity and exercise in this condition. High-fat diet-induced obese and lean C57BL/6J mice were allocated to sedentary or exercised groups. The inflammatory profiles and phenotypes of their peritoneal macrophages were assessed by flow cytometry in the presence or absence of the selective β2-adrenergic receptor agonist terbutaline. β2-adrenergic activation caused global phenotypic anti-inflammatory effects in lean and obese sedentary mice, which were more drastic (also including anti-inflammatory effects on the cytokine profile) in obese animals. In exercised lean and obese animals, this anti-inflammatory effect is weaker and only evident by decreased iNOS and IL-8 expression, without changes in the anti-inflammatory markers. Therefore, β2-adrenergic activation leads to anti-inflammatory effects, but these effects are modulated by obesity in sedentary conditions, as well as by regular exercise; but not by obesity in trained conditions.
Highlights
Obesity is considered a low-grade inflammatory condition, that is, a chronic systemic condition involving elevated systemic concentrations of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-1RA, and other inflammatory mediators such as C-reactive protein (CRP) [1,2,3,4,5,6]
Catecholamines secreted by the sympathetic nervous system (SNS) and the adrenal glands are endogenous adrenergic agonists that are crucial in regulating metabolism as well as most of the immune response mechanisms, including systemic and local release of inflammatory cytokines and chemokines and the innate response [7,11,12,13,14,15,16]
Published investigations have already shown that this high-fat diet (HFD) protocol causes obesity in this mouse strain: mice present high fasting glucose concentration (>250 macrophages in(Kj/day) response to terbutaline (mg/dL) as the recommended threshold [29]) and elevated levels of triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), and calculated low-density lipoprotein cholesterol
Summary
Obesity is considered a low-grade inflammatory condition, that is, a chronic systemic condition involving elevated systemic concentrations of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-1RA, and other inflammatory mediators such as C-reactive protein (CRP) [1,2,3,4,5,6]. Immune-neuroendocrine responses involving the HPA axis, the SNS, and macrophages can be different in healthy individuals, in patients with inflammatory pathologies, and/or after pathogen challenge. This regulation by exercise depends on each individual’s basal set-point, being anti-inflammatory mainly (or only) in the case of a highly inflammatory status [27]. Regular exercise can induce anti-inflammatory benefits by switching the inflammatory phenotype of monocytes and macrophages in obese individuals [24,26] This way, exercise programs must be aimed at achieving a decrease in dysregulated levels of inflammatory mediators together with optimal phenotypic transitions between M1 and M2 macrophages [8,16]. To the best of our knowledge, this is the first investigation to comprehensively analyze the influence of exercise and obesity in β2-adrenergic regulation of the inflammatory profile of macrophages
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