Exercise-induced ß-hydroxybutyrate promotes Treg cell differentiation to ameliorate colitis in mice.

Increasing attention is being paid to the mechanistic investigation of exercise-associated chronic inflammatory disease improvement. Ulcerative colitis (UC) is one type of chronic inflammatory bowel disease with increasing incidence and prevalence worldwide. It is known that regular moderate aerobic exercise (RMAE) reduces the incidence or risk of UC, and attenuates disease progression in UC patients. However, the mechanisms of this RMAE's benefit are still under investigation. Here, we revealed that ß-hydroxybutyrate (ß-HB), a metabolite upon prolonged aerobic exercise, could contribute to RMAE preconditioning in retarding dextran sulfate sodium (DSS)-induced mouse colitis. When blocking ß-HB production, RMAE preconditioning-induced colitis amelioration was compromised, whereas supplementation of ß-HB significantly rescued impaired ß-HB production-associated defects. Meanwhile, we found that RMAE preconditioning significantly caused decreased colonic Th17/Treg ratio, which is considered to be important for colitis mitigation; and the downregulated Th17/Treg ratio was associated with ß-HB. We further demonstrated that ß-HB can directly promote the differentiation of Treg cell rather than inhibit Th17 cell generation. Furthermore, ß-HB increased forkhead box protein P3 (Foxp3) expression, the core transcriptional factor for Treg cell, by enhancing histone H3 acetylation in the promoter and conserved noncoding sequences of the Foxp3 locus. In addition, fatty acid oxidation, the key metabolic pathway required for Treg cell differentiation, was enhanced by ß-HB treatment. Lastly, administration of ß-HB without exercise significantly boosted colonic Treg cell and alleviated colitis in mice. Together, we unveiled a previously unappreciated role for exercise metabolite ß-HB in the promotion of Treg cell generation and RMAE preconditioning-associated colitis attenuation.

Enhancing cognitive performance and mitigating dyslipidemia: the impact of moderate aerobic training on sedentary older adults.

BACKGROUND: The present study aimed to evaluate the effects of 24 weeks of moderate aerobic exercise on lipids and lipoprotein levels; Lipo (a) markers, and their association with cognitive performance in healthy older adults. METHODS: A total of 150 healthy subjects (100 males and 50 females; age range: 65-95 years) were recruited for this study. Based on the LOTCA test score, subjects were classified into two groups: the control group (n = 50) and the cognitive impairment group (n = 100). Cognitive functioning, leisure-time physical activity (LTPA), lipid profile, total cholesterol, TG, HDL-c, LDL-C, and lipo(a) were assessed at baseline and post-24-week aerobic exercise interventions using LOTCA battery, pre-validated Global Physical Activity Questionnaire (GPAQ) version II, colorimetric, and immunoassay techniques, respectively. RESULTS: Significant improvements in cognitive function and modulation in lipid profile and lipoprotein (a) markers were reported in all older subjects following 24 weeks of moderate exercise. LOTCA-7-sets scores significantly correlated with physical activity status and the regulation of lipids and Lipo (a) markers. Physically active persons showed higher cognitive performance along with a reduction in the levels of T-Cholest., TG, LDL-C, Lipo (a), and an increase in the levels of HDL-C and aerobic fitness VO2max compared with sedentary participants. Cognitive performance correlated positively with increased aerobic fitness, HDL-C, and negatively with T-Cholest., TG, LDL-C, and Lipo (a). However, a significant increase in the improvement of motor praxis, vasomotor organization, thinking operations, attention, and concentration were reported among older adults. CONCLUSIONS: The study findings revealed that supervised moderate aerobic training for 24 weeks significantly enhances cognitive functions via mitigating older adults' lipid profiles and lipoprotein (a). Cognitive performance is positively correlated with aerobic fitness and HDL-C level and negatively with T-Cholest., TH, LDL-C, and Lipo (a).

Arterial Stiffness by Aerobic Exercise Is Related with Aerobic Capacity, Physical Activity Energy Expenditure and Total Fat but not with Insulin Sensitivity in Obese Female Patients with Type 2 Diabetes

BACKGROUND: Arterial stiffness is an important factor in atherosclerosis. Thus we examined whether aerobic exercise could reduce arterial stiffness in obese women with type 2 diabetes without diabetic complication. METHODS: A total of 35 women with type 2 diabetes (body mass index, 26.6+/-2.8 kg/m2; age, 56.4+/-1.9 years; duration of diabetes, 4.7+/-4.8 years) were assigned to aerobic exercise group (AEG) or control group (CG). AEG completed a 12-week exercise program (3.6 to 5.2 metabolic equivalents, 3 day/week, 60 min/day), with their exercise activities monitored by accelerometers. We measured abdominal total fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) by computed tomography, insulin sensitivity by insulin tolerance test (K(ITT)), and augmentation index (AIx) by SphygmoCor at baseline and at the end of the 12-week program. RESULTS: The AIx was improved in the AEG compared with the CG (P<0.001). The percent change of AIx had significant correlation with the improvement of physical activity energy expenditure (PAEE), aerobic capacity, TFA, and SFA (r=-0.416, P=0.013; r=0.560, P<0.001; r=0.489, P=0.003; r=0.531, P=0.001, respectively), but not with insulin sensitivity, energy intake, or VFA. CONCLUSION: Improvement in aortic stiffness by aerobic exercise is related with the improvement of aerobic capacity, PAEE, and total fat but not with insulin sensitivity or energy intake in obese women with type 2 diabetes.