Resistance exercise training augments the immunomodulatory adaptations to aerobic high‐intensity interval training

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ABSTRACT

To compare the effectiveness of different types of high‐intensity interval training (HIIT) on meta‐inflammation during obesity, TLR4 pathway activities were assessed following a 10‐week randomized trial. 30 young females with overweight and obesity were randomly allocated to aerobic HIIT (HIIT/AE) or resistance exercise in HIIT (HIIT/RE) and performed a 28‐minute (4 × 4 min) in each session. During each interval, the HIIT/AE performed four minutes of all‐extremity cycling, whereas the HIIT/RE completed four minutes of combined resistance exercises and all‐extremity cycling. The TLR4 pathway gene expression was measured for the TLR4 receptor, downstream adaptors (TIR domain‐containing adaptor‐inducing interferon‐β (TRIF) and myeloid differentiation factor (MYD) 88), transcriptional factors (nuclear factor kappa B (NF‐κB), and interferon regulatory factor (IRF) 3), and its negative regulator (tumor necrosis factor (TNF) a‐induced protein 3 (TNFAIP3)). The serum levels of TNFα, interferon (IFN) γ, interleukin (IL)‐10, and adiponectin were measured. We found that TLR4 (HIIT/RE: 0.6 ± 0.43 vs. HIIT/AE: 1.24 ± 0.82, p = 0.02), TRIF (HIIT/RE: 0.51 ± 0.4 vs. HIIT/AE: 3.56 ± 0.52, p = 0.001), and IRF3 (HIIT/RE: 0.49 ± 0.42 vs. HIIT/AE: 0.6 ± 0.89; p = 0.04) levels were significantly downregulated in HIIT/RE compared to the HIIT/AE, with a significant reduction in serum levels of TNFα (pg/ml) (HIIT/RE: 22.5 ± 11.3 to 6.3 ± 5.3 vs. HIIT/AE: 19.16 ± 20.8 to 13.48 ± 21.7, p = 0.04) and IFNγ (pg/ml) (HIIT/RE: 43.5 ± 20.6 to 37.5 ± 4.3 vs. HIIT/AE: 37.6 ± 5.6 to 68.1 ± 22.5, p = 0.03). Adiponectin and IL‐10 levels did not significantly differ between the two groups. Thus, resistance exercise training augments the immunomodulatory adaptations to HIIT and should be prescribed to people at risk of cardiometabolic disease.

Highlights

HIIT in combination with resistance exercise looks more effective than HIIT alone to target TLR4‐mediated inflammation in individuals with overweight and obesity.
HIIT/RE induces a different effect on two downstream cascades of TLR4, leading to a greater overall reduction of TRIF‐dependent pathway activities compared to MYD88.
Both HIIT protocols show comparable effects on the negative regulatory protein TNFAIP3 gene expression.

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During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.

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Regular exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, in part because exercise exerts anti-inflammatory effects. However, these effects are also likely to be responsible for the suppressed immunity that makes elite athletes more susceptible to infections. The anti-inflammatory effects of regular exercise may be mediated via both a reduction in visceral fat mass (with a subsequent decreased release of adipokines) and the induction of an anti-inflammatory environment with each bout of exercise. In this Review, we focus on the known mechanisms by which exercise - both acute and chronic - exerts its anti-inflammatory effects, and we discuss the implications of these effects for the prevention and treatment of disease.

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Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids

Marcelo Rogero, Philip C. Calder (2018)

Obesity leads to an inflammatory condition that is directly involved in the etiology of cardiovascular diseases, type 2 diabetes mellitus, and certain types of cancer. The classic inflammatory response is an acute reaction to infections or to tissue injuries, and it tends to move towards resolution and homeostasis. However, the inflammatory process that was observed in individuals affected by obesity and metabolic syndrome differs from the classical inflammatory response in certain respects. This inflammatory process manifests itself systemically and it is characterized by a chronic low-intensity reaction. The toll-like receptor 4 (TLR4) signaling pathway is acknowledged as one of the main triggers of the obesity-induced inflammatory response. The aim of the present review is to describe the role that is played by the TLR4 signaling pathway in the inflammatory response and its modulation by saturated and omega-3 polyunsaturated fatty acids. Studies indicate that saturated fatty acids can induce inflammation by activating the TLR4 signaling pathway. Conversely, omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, exert anti-inflammatory actions through the attenuation of the activation of the TLR4 signaling pathway by either lipopolysaccharides or saturated fatty acids.