Endurance training induces depot-specific changes in IL-10/TNF-α ratio in rat adipose tissue

Abstract

White adipose tissue (WAT) is the source of pro- and anti-inflammatory cytokines and recently, it has been recognized as an important source of interleukin 10 (IL-10). Acute physical exercise is known to induce an anti-inflammatory cytokine profile, however, the effect of chronic physical exercise on the production of IL-10 by WAT has never been examined. We assessed IL-10 and TNF-α concentration in WAT of rats engaged in endurance training. Animals were randomly assigned to either a sedentary control group (S, n = 7) or an endurance trained group (T, n = 8). Trained rats ran on a treadmill 5 days/wk for 8 wk (55–65% VO_2max). Detection of IL-10 and TNF-α protein and mRNA expression, as well as the gene expression of PPAR-γ, and immunocytochemistry to detect mononuclear phagocytes were carried out. A reduction in absolute retroperitoneal adipose tissue (RPAT) weight in T (44%; p < 0.01), when compared with S was observed. IL-10 concentration was increased (1.5-fold, p < 0.05), to a higher extent than that of TNF-α (66%, p < 0.05) in the mesenteric adipose tissue (MEAT) of the trained group, while no change related to training was observed in RPAT. In MEAT, IL-10/TNF-α ratio was increased in T, when compared with S (30%; p < 0.05). PPAR-γ gene expression was increased in T (1.1-fold; p < 0.01), when compared with S in the same adipose depot. No monocyte infiltration was found. In conclusion, exercise training induced increased IL-10 expression in the mesenteric depot, resulting in a modified IL-10/TNF-α ratio. We also conclude that WAT presents a depot-specific response to endurance training regarding the studied aspects.

Introduction

The current view of white adipose tissue (WAT) function considers its secretory properties in addition to the storage of lipids [1]. WAT actively secretes various bioactive peptides, termed “adipokines”, which act locally and distally, with autocrine, paracrine and endocrine effects [2]. Nevertheless, the physiology, metabolism and function of WAT vary in a depot-specific manner, as reviewed by [3]. Therefore, marked differences in gene expression amongst depots are reported both for rodents [4] and humans [5], and cytokine secretion is also heterogeneous [3]. The anti-inflammatory interleukin 10 (IL-10), for instance, secreted by human subcutaneous and visceral adipose depots, is more expressed in the latter [6], while the secretion of tumor necrosis factor α (TNF-α), an important pro-inflammatory cytokine, with a major role in the regulation of cellular processes [7], is secreted in a similar way by the human subcutaneous and visceral adipose depots [8]. TNF-α is the most-studied cytokine in WAT, with the greatest mRNA expression being found in the adipocyte per se [9]. This cytokine is involved in metabolic, physiological and immunological regulation in this tissue, and plays a pivotal role in relation to the production of several cytokines (e.g. IL-10) and many other adipokines in WAT, such as leptin [10], [11].

IL-10, secreted by adipocytes, stromal vascular fraction and tissue matrix of WAT [12], acts as a natural antagonist to TNF-α, inhibiting nuclear factor kappa B (NF-κB) signaling through the preservation of inhibitory factor kappa B (IκB) [13]. Thus, due to its anti-inflammatory potential, the therapeutic use of IL-10 has also been tested in many chronic inflammatory diseases in which TNF-α is believed to play a prominent role (e.g. rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and cardiac allograft rejection) [14]. Interleukin 6 (IL-6-a cytokine related both to acute phase reaction and anti-inflammation) secretion [6], is also heterogeneous, being higher in the visceral depots. IL-6, together with TNF-α, have been the focus of most of the research related to cytokine production by the adipose tissue, as it also potentially appears as an important molecule in the communication between WAT and the hypothalamus, associated with the regulation of energy balance [15], in concomitance to leptin. The expression of interleukin 1β (IL1-β, another important pro-inflammatory product of WAT) also seems to present depot variation [16].

Several studies [17], [18], [19] have shown an anti-inflammatory effect of acute physical exercise, characterized through increased circulating concentrations of IL-10, IL-1 receptor antagonist (IL-1ra), soluble receptor of TNF (TNFRs), among other alterations. Fewer studies addressed the effect of chronic exercise on the same parameters with respect to the contribution of WAT, and no study, to our knowledge, has compared cytokine production in different WAT depots in trained healthy rats.

Therefore, considering the important role of WAT in the synthesis and secretion of cytokines, and the well established capacity of moderate intensity exercise to induce an anti-inflammatory response, we have sought to examine the effects of endurance training upon the expression of cytokines in rodent retroperitoneal and mesenteric depots. The results show that IL-10/TNF-α ratio in WAT, which has been pointed out as an indicator of inflammatory status [20], [21] presents a depot-specific response to endurance training.