Acute effect of exercise intensity on circulating FGF-21, FSTL-1, cathepsin B, and BDNF in young men.

Background/objectives: Exercise intensity is potentially an important regulator of various exerkines secretion, but the optimal exercise intensity to increase and sustain exerkines levels, including FGF-21, FSTL-1, cathepsin B, and BDNF in humans, has not yet been fully elucidated. This study aimed to examine the circulating levels of FGF-21, FSTL-1, cathepsin B, and BDNF according to the exercise intensity. Methods: Nine young men (24.0 ± 0.4 years old) performed 4 different experimental sessions at 1-week intervals: 1) a control session (CTRL; no exercise); 2) moderate-intensity continuous exercise (MICE, 55% HRR); 3) vigorous-intensity continuous exercise (VICE, 85% HRR); and 4) high-intensity interval exercise (HIIE, 4 repetitions of a 30-s of "all out" cycling workout followed by a 4-min recovery). Blood samples were collected at 4 different time points (pre-exercise, immediately post-exercise, 30 min post-exercise, and 90 min post-exercise). Results: Serum FGF-21, FSTL-1, cathepsin B, and BDNF were higher in HIIE than in CTRL immediately post-exercise, and FSTL-1, cathepsin B, and BDNF were higher in HIIE than in MICE immediately post-exercise (P < 0.05). The AUC for FGF-21, FSTL-1, and BDNF was higher in HIIE than in CTRL, and the AUC for FGF-21 and BDNF was higher in HIIE than in MICE (P < 0.05). Furthermore, the change in blood lactate was positively correlated with the changes in all exerkines. Conclusions: This study demonstrates that acute HIIE effectively increases serum FGF-21, FSTL-1, cathepsin B, and BDNF compared to MICE. Therefore, the secretion of exerkines, including FGF-21, FSTL-1, cathepsin B, and BDNF may be exercise intensity-dependent.

Chronic voluntary wheel running exercise ameliorates metabolic dysfunction via PGC-1α expression independently of FNDC5/irisin pathway in high fat diet-induced obese mice.

Exercise is an effective intervention to ameliorate metabolic diseases including obesity and insulin resistance, but the mechanisms involved in the metabolic amelioration have not yet been fully elucidated. This study aimed to determine whether AMPK-SIRT1-PGC-1α-FNDC5/Irisin-UCP1 expression is activated and whether metabolic dysfunction is ameliorated by chronic voluntary wheel running (VWR) in high-fat diet (HFD) induced obese mice. C57BL6J mice were randomly assigned into three groups at the age of 7 weeks for 10 weeks: normal chow diet (CON) group, HFD group, and HFD + VWR group. Chronic VWR ameliorates metabolic parameters and leads to increases in the expression of PGC-1α in the gastrocnemius muscle in HFD-induced obese mice. In contrast, the expression of AMPKα, SIRT1, and FNDC5, or circulating irisin levels did not lead to alteration. Improvement of metabolic health was partly mediated via PGC-1α expression by chronic VWR, but not FNDC5/Irisin pathway in HFD-induced obese mice.

The Kv7 channel activator, retigabine, induces vasorelaxation via an endothelial-independent pathway in male mouse aorta.

PURPOSE: Previous studies have indicated that Kv7 channels have an important role in the regulation of blood vessel reactivity, including in the coronary, renal, and cerebral arteries. The present studies examined whether Kv7 channels regulated vascular reactivity in the mouse aorta and investigated the mechanisms involved in the reactivity. METHODS: Wild-type (WT) male C57BL/6 mice, between 10 and 15 weeks old, were used in this study. The vascular function of the aorta in WT male mice was assessed by using a pin myography system (Model 620; DMT, Denmark). RESULTS: Vasorelaxation by an endothelial-dependent vasodilator, acetylcholine (ACh, 1 nM - 10 µM) and an endothelial-independent vasodilator, sodium nitroprusside (SNP, 1 nM - 10 µM) was induced in the aorta in a dose-dependent manner. Pre-incubation with the nitric oxide synthase inhibitor, L-NAME (100 µM, 20 min), completely abolished ACh-induced vasorelaxation, but did not block retigabine-induced vasorelaxation, which suggested that retigabine caused vasorelaxation in the aorta via smooth muscle activation rather than via endothelial cells. Pre-application of the Kv7 channel blocker, linopirdine (10 µM), resulted in a greater contractile response compared with that induced by vehicle in the aorta. In addition, pre-incubation with linopirdine (10 µM, 20 min) reduced retigabine-induced vasorelaxation (1-50 µM). CONCLUSION: This study has provided evidence that Kv7 channels may play a role in the regulation of aortic blood flow via smooth muscle activation.