Caffeine is an adenosine A_2A receptor (ADORA2A) antagonist with ergogenic and anti-inflammatory effects. Previous studies have reported that the ADORA2A gene regulates glutamate metabolism and immune responses, with the ADORA2A rs5751876 TT genotype (with high sensitivity to caffeine) showing larger ergogenic effect following caffeine ingestion. We therefore hypothesized that the TT genotype would be associated with greater anti-inflammatory effects of caffeine in response to exercise, and with higher coffee intake in physically active individuals. The aim of the present study was twofold: (1) to investigate the association of the ADORA2A variant with the anti-inflammatory effects of caffeine in response to intense resistance exercise (RE), and (2) to analyze the association of the rs5751876 with coffee intake in physically active individuals (n = 134). Fifteen resistance-trained athletes participated in a randomized, double-blind, placebo-controlled cross-over study, where they consumed 6 mg/kg of caffeine or placebo one hour prior to performing an RE protocol. Blood samples were taken immediately from the arterial vein before, immediately after, and 15 min after RE for the analysis of inflammatory markers myeloperoxidase (MPO) and acetylcholinesterase (AChE). We found that the ADORA2A TT genotype carriers experienced lower exercise-induced inflammatory responses (p < 0.05 for AchE) when compared to the C allele carriers (i.e., CC/CT) one hour following the ingestion of caffeine. Furthermore, the ADORA2A TT genotype was positively associated with coffee intake (p = 0.0143; irrespective of CYP1A2 rs762551 polymorphism). In conclusion, we found that the ADORA2A gene polymorphism is associated with anti-inflammatory effects of caffeine in response to resistance exercise, as well as with habitual coffee intake in physically active individuals.

The aim of this study was to investigate the combined effects of vitamin D3 supplementation and aerobic training on regulating the autophagy process in rats with type 2 diabetic induced by a high-fat diet and streptozotocin. A total of 40 Wistar rats were divided into five groups: normal control (NC), diabetic control (DC), diabetic + aerobic training (DAT), diabetic + vitamin D3 (DVD), and diabetic + aerobic training + vitamin D3 (DVDAT). The rats underwent eight weeks of aerobic training with an intensity of 60% maximum running speed for one hour, along with weekly subcutaneous injections of 10,000 units of vitamin D3. The protein levels of different autophagy markers were assessed in the left ventricular heart tissue. The results showed that the protein levels of AMPK, pAMPK, mTOR, and pmTOR were significantly lower in the DC group compared to the NC group. Conversely, the levels of ULK, Beclin-1, LC3II, Fyco, and Cathepsin D proteins were significantly higher in the DC group. However, the interventions of aerobic training and vitamin D3 supplementation, either individually or in combination, led to increased levels of AMPK, pAMPK, mTOR, and pmTOR, and decreased levels of ULK, Beclin-1, LC3II, Fyco, and Cathepsin D (p < 0.05). Additionally, the aerobic capacity in the DAT and DVDAT groups was significantly higher compared to the NC, DC, and DVD groups (p < 0.05). These findings suggest that type 2 diabetes is associated with excessive autophagy in the left ventricle. However, after eight weeks of vitamin D3 supplementation and aerobic training, a significant reduction in excessive autophagy was observed in rats with type 2 diabetes.

Introduction: This study investigated the effect of vitamin D3 injection combined with high‐intensity interval training on cell signaling pathways involved in excessive autophagy, specifically the mTOR (mechanistic target of rapamycin)–Beclin‐1–Fyco‐1 (FYVE and coiled‐coil domain‐containing protein 1)–cathepsin D pathway, in the heart tissue of Type 2 diabetes–induced rats. Method: In this experimental study, 32 male Wistar rats were fed a high‐fat diet for 6 weeks to induce Type 2 diabetes, followed by a single subcutaneous injection of 35 mg/kg streptozotocin (STZ). The rats were then randomly assigned to one of four groups: (1) diabetes control (DC), (2) diabetes + HIIT (DT), (3) diabetes + vitamin D3 (DV), and (4) diabetes + HIIT + vitamin D3 (DTV). HIIT sessions were conducted for 8 weeks, five times per week, at an intensity of 85%–95% of maximum running speed ( V _max ), while vitamin D3 was administered weekly via subcutaneous injection at a dose of 10,000 IU/kg. Twenty‐four hours after the intervention period, heart and left ventricular tissues were collected for analysis of the levels of autophagy signaling proteins mTOR, phosphorylated mechanistic target of rapamycin (pmTOR), Beclin‐1, Fyco‐1, and cathepsin D. Results: Two‐way ANOVA revealed that Type 2 diabetes significantly increased the levels of Beclin‐1, Fyco‐1, and cathepsin D ( p < 0.001) while significantly reducing the levels of mTOR and pmTOR ( p < 0.001). HIIT, vitamin D3 injection, and their combined treatment significantly decreased the levels of Beclin‐1, Fyco‐1, and cathepsin D and increased the levels of mTOR and pmTOR compared to the diabetes control group ( p < 0.001). Conclusion: Type 2 diabetes increases autophagy in the left ventricle, marked by altered levels of key autophagy proteins. HIIT and vitamin D3 injections mitigate these effects by enhancing mTOR signaling and reducing excessive autophagy. These interventions show promise as nonpharmacological strategies to improve cardiac health in Type 2 diabetes and could be incorporated into clinical and rehabilitation programs.

Asprosin, a protein that enhances insulin resistance by stimulating hepatic glucose secretion, is linked to obesity, metabolic disorders, and cardiovascular diseases. This systematic review and meta‐analysis investigate the influence of exercise training (ET) on circulating concentrations of asprosin. A systematic search of PubMed, Web of Science, and Google Scholar databases was conducted for all randomized controlled clinical trials from January 2016 to November 2024. A total of 431 relevant articles were retrieved and screened according to the study population, intervention method, and study type, resulting in the selection of 14 articles for the meta‐analysis. All statistical results were analyzed using Comprehensive Meta‐Analysis Software version 2 (CMA2). The overall effect size, using Hedges' g, based on the random effects model for asprosin with ET, was −1.70 (95% CI −2.17 to −1.23, p = 0.0001). A decrease in asprosin concentration was observed with all types of ET including aerobic training (AT, H = −1.71, p = 0.0001), high‐intensity interval training (HIIT, H = −1.81, p = 0.001), and resistance training (RT, H = −1.62, p = 0.0001). Furthermore, subgroup analysis showed differences in asprosin based on body mass index (Q‐value = 11.09, df = 2, p = 0.004) and health status of the subjects (Q‐value = 12.64, df = 2, p = 0.002); however, there were no differences based on sex (p = 0.67), types (p = 0.96), and duration (p = 0.34) of training. Our findings suggest that ET is associated with a decrease in circulating asprosin that could have a beneficial effect in preventing metabolic disease that is enhanced with obesity. Systematic review registration PROSPERO: CRD42023468813.

Coenzyme Q10 (CoQ10), a vital mitochondrial antioxidant, may enhance cardiovascular recovery and delay fatigue in athletes. This double-blind, randomized,