Direct assessment of leukocyte signalling and cytokine secretion reveals exercise intensity-dependent reductions in anti-inflammatory cytokine action.

Circulating interleukin (IL)-6 and IL-10 concentrations are widely used to evaluate the anti-inflammatory effects of exercise but do not capture cytokine action at the cellular level. Whether and how acute exercise impacts anti-inflammatory cytokine action in humans is unknown. To determine how exercise intensity and pattern impact IL-6 and IL-10 action in blood leukocytes, 16 active adults (eight males/eight females; age: 30 ± 3 years; body mass index: 22.8 ± 2.3 kg/m2; V ̇ O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ : 51 ± 6 mL/kg/min) completed a no-exercise control condition (CTL) or isocaloric bouts of cycling performed below (moderate continuous exercise; MCE) or above (heavy continuous or heavy intermittent exercise; HCE or HIE, respectively) lactate threshold. Venous blood (before, after, 30 min after and 90 min after exercise) was analysed for immune cell subpopulations, plasma cytokine concentrations, anti-inflammatory cytokine action and monocyte phenotype. Exercise induced rapid leukocytosis (P < 0.001) and increased plasma IL-6 (P < 0.001), IL-10 (P = 0.0145) and tumour necrosis factor-⍺ (TNF-⍺) (P = 0.0338) concentrations in an intensity-dependent manner (HCE and/or HIE vs. CTL). These systemic changes coincided with a diminished ability of IL-10/6 to phosphorylate STAT3 (P < 0.001) and inhibit TNF-⍺ secretion (P = 0.0238) in blood leukocytes following HCE and HIE. Monocyte polarization experiments revealed lower CD80 [MCE (P = 0.0933) and HIE (P = 0.0187) vs. CTL] and a tendency for higher CD163 expression (HCE vs. CTL, P = 0.0985), suggesting that hyporesponsiveness to anti-inflammatory cytokine action does not impede the ability of exercise to promote an anti-inflammatory monocyte phenotype. These findings provide novel insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise. KEY POINTS: Circulating cytokine concentrations are frequently used to evaluate the anti-inflammatory effects of exercise but may not capture changes in cytokine action occurring at the cellular level. We directly assessed anti-inflammatory cytokine action - measured using a combination of intracellular signalling and cytokine secretion ex vivo - in distinct immune cell subpopulations after acute calorie-matched exercise bouts differing in intensity and pattern. Anti-inflammatory cytokine action was blunted following higher intensity exercise despite corresponding increases in circulating cytokine concentrations and immune cell counts. Changes in cytokine action were not explained by changes in cytokine receptor expression on circulating immune cells. Our findings provide new insights into the immunomodulatory effects of exercise in humans and highlight the importance of directly measuring cellular cytokine action when evaluating the anti-inflammatory effects of exercise.

Effects of acute resistance exercise with different loads on appetite, appetite hormones and autonomic nervous system responses in healthy young men.

Although the effect of continuous aerobic exercise on the appetite has been widely explored, the influence of resistance exercise (RE) with different variables, including training loads, training volume, and inter-set rest, on appetite responses requires further investigation. This study examined the importance of training load in RE-induced appetite regulation, with the total training volume and inter-set rest equalized. In total, 11 healthy young men (age = 23 ± 2 years, body mass index = 22 ± 2 kg/m2) were included. Participants completed 3 trials, namely moderate-load RE (MOD; 4 sets of 8 repetitions at 85% 8RM), low-load RE (LOW; 4 sets of 15 repetitions at 45% 8RM), and a control (CON; no exercise), in a randomized, crossover design. Subjective appetite ratings; concentrations of ghrelin, peptide YY (PYY), and lactate; and the autonomic nervous system activity were evaluated before exercise and 1 h after exercise. The hunger and predicted food consumption ratings, and ghrelin concentrations immediately after exercise were significantly lower in the MOD and LOW trials (p < 0.05 vs. CON). The PYY and lactate concentrations immediately after exercise were significantly higher in the MOD and LOW trials (p < 0.05 vs. CON). Heart rate variability recovery was slower in the MOD trial. These findings suggest that both moderate-load and low-load RE at equal training volumes and inter-set rest induce similar responses on hunger suppression and orexigenic signals, except for the slower recovery of autonomic modulation after moderate-load RE. Our results suggest that when individuals aim to potentiate appetite suppression after a bout of RE, both moderate- and low-load RE could be applied.

Supervised high-load resistance training for improving muscle strength and quality in prediabetic older adults: A pilot randomized controlled trial.

OBJECTIVE: To investigate the effects of high- and low-load supervised, volume-matched resistance training (RT) on body composition, muscle function, and functional capacity in older adults with prediabetes. METHODS: Older adults with prediabetes were recruited and randomly assigned to high-load RT (n = 13), low-load RT (n = 12), or control groups (n = 12). RESULTS: No significant differences were observed in body composition at postintervention. High-load and low-load RT groups exhibited significant improvements in functional tests at postintervention compared with the control group. The high-load RT group exhibited a greater improvement in muscle strength and muscle quality at postintervention compared with the low-load RT group. CONCLUSION: Supervised RT is useful in the prevention of muscle functional loss in older adults with prediabetes. High-load RT is superior for enhancing muscle strength and muscle quality, despite a similar increase in functional capacity.

Effect of Progressive Resistance Training on Circulating Adipogenesis-, Myogenesis-, and Inflammation-Related microRNAs in Healthy Older Adults: An Exploratory Study.

BACKGROUND: Functional and physiological adaptations induced by resistance training have been extensively studied in older adults. However, microRNA (miRNA) as the novel regulator in protective effects remains poorly understood. OBJECTIVE: The purpose of an exploratory study was to analyze the response of a panel of circulating miRNAs to adaptations mediated by resistance training. METHODS: Ten healthy older adults (age: 67.6 ± 2.2 years, 7 women and 3 men) without previous experience in resistance training were recruited. Blood samples were collected at baseline and after a 12-week resistance training. Next-generation sequencing was used to determine circulating miRNA responses to chronic resistance training. RESULTS: After the 12-week training, physical functions including grip strength, lower body strength and endurance, and walking capacity were improved in the older adults, while the serum levels of leptin (from 18.1 ± 20.0 to 14.9 ± 17.6 ng/mL, p = 0.029) and tumor necrosis factor alpha (TNFα; from 4.4 ± 0.6 to 4.0 ± 0.6 pg/mL, p < 0.001) were significantly decreased. In addition, adipogenesis-related miRNAs (miR-103a-3p, -103b, -143-5p, -146b-3p, -146b-5p, -17-5p, -181a-2-3p, -181b-5p, -199a-5p, -204-3p, and -378c), anti-adipogenesis-related miRNAs (miR-155-3p, -448, and -363-3p), myogenesis-related miRNAs (miR-125b-1-3p, -128-3p, -133a-3p, 155-3p, -181a-2-3p, -181b-5p, -199a-5p, -223-3p, and -499a-5p), and inflammation-related miRNAs (miR-146b-3p, -146b-5p, -155-3p, -181a-2-3p, and -181b-5p) were changed significantly in the older adults after training (fold change >2, p < 0.05). The log2 fold change of miRNA-125-1-3p was inversely correlated with delta walking time (R = -0.685, p = 0.029) and change in insulin-like growth factor 1 (R = -0.644, p = 0.044). CONCLUSIONS: Our results can help explain the link between specific circulating miRNAs and beneficial effects of resistance training on functional and physiological adaptations in older adults.

Activation of inflammatory pathways in PBMCs linking type 2 diabetes in older adults without obesity.

The mechanism that underlies the dysregulation of glucose metabolism in older adults without obesity has yet to be thoroughly understood. This study investigated the risk of developing Type 2 diabetes (T2D) in older adults without obesity (BMI: 18.5 to <25 kg/m2). Data on glucose levels (measured by an oral glucose tolerance test), body composition, physical activity level, lipid profile, inflammatory cytokines, and nuclear factor kappa B (NF-κB) and Sirtuin 1 (SIRT1) signaling pathways in peripheral blood mononuclear cells (PBMCs) in older adults with normal glucose tolerance (NGT, n = 17) and those with prediabetes (n = 20) or T2D (n = 8) were gathered. As expected, participants with T2D exhibited higher insulin resistance; ß-cell dysfunction; and higher levels of triglycerides and tumor necrosis factor-α (TNF-α) than those with NGT. No differences in physical activity, lean mass, body fat, or cholesterol were observed between the NGT, prediabetes, and T2D groups. Downregulation of SIRT1 and activation of NF-κB signaling in PBMCs were observed in the T2D group. Increased phosphorylation of NF-κB and low SIRT1 protein expression in PBMCs were associated with insulin resistance and ß-cell dysfunction. NF-κB and its upstream inhibitor IκBα were positively and inversely correlated with TNF-α, respectively. SIRT1 expression was positively correlated with IL-10. Activation of NF-κB signaling pathways and downregulation of SIRT1 in PBMCs were associated with the inflammatory milieu in older adults without obesity.

Effects of volume-matched resistance training with different loads on glycemic control, inflammation, and body composition in prediabetic older adults.

The purpose of the investigation was to examine the influence of resistance training (RT) with equal volume and varying load on glycemic control, inflammation, and body composition in non-obese prediabetic older adults. Non-obese older adults with prediabetes were randomized into 2 groups, high-load (80% of 1RM) and low-load (40% of 1RM) RT (n = 12/group), both with the same training volume. Oral glucose tolerance test (OGTT) and blood samples were collected at baseline and again after 10 weeks of RT. Fasting blood glucose (103.8 vs. 99.9 mg/dL) and the area under the curve (AUC) of OGTT (0-30 min) decreased significantly in older adults with prediabetes after 10 weeks of volume-matched RT (p < 0.05). Serum levels of MCP-1 (138.7 vs. 98.5 pg/mL) and TNF-α (1.8 vs. 1.3 pg/mL) showed significant decrease after 10 weeks of high-load RT (p < 0.05). There were no changes in IL-10, IL-6, and CRP levels in both groups. Leptin showed significant decrease after 10 weeks of low-load RT (p < 0.05). Changes in fasting glucose and AUC of OGTT (0-120 min) were positively correlated with changes in MCP-1 and TNF-α (p < 0.05). Lean body mass (39.6 vs. 40.3 kg) increased significantly after 10 weeks of volume-matched RT (p < 0.05). Results indicate that equal-volume RT at different loads is beneficial to glycemic control and muscle growth, and high-load RT shows more prominent anti-inflammatory effects. Novelty: Short-term high-load resistance training can help older adults bring their blood sugar level back to normal. High-load resistance training attenuates aging-associated chronic inflammation.