Beneficial cardiovascular-renal effects of exercise on aging male and female obese TallyHo/Jng mice

The benefits of aerobic exercise on cardiorenal health in aging, insulin-resistant individuals are not fully understood. We hypothesized that chronic treadmill exercise (aerobic training) of overweight aging (10-month old) insulin-resistant TallyHo/Jng (TH) mice (prone to type 2 diabetes) would improve the comprehensive cardiovascular phenotype and metabolism. Male (M) and female (F) TH mice (n = 10/group) underwent treadmill running exercise (Ex, 10-19 meters/min) for 15-30 minutes, 4X/week or remained sedentary (Sd) for 9 weeks. Final body weights were 20 and 30% lower in M and F Ex, relative to same sex Sd groups, respectively. Ultrasound conducted a week prior to euthanizing showed renal blood flow (external velocity, pulse wave doppler) was significantly increased by Ex on average 26 and 24% in M and F, respectively (2-way ANOVA for Ex, p = 0.0089). With regard to cardiac features, while cardiac output was not significantly different between groups, stroke volume was increased in both sexes by Ex (9% in M, 5% in F). Whereas, cardiac ejection fraction and fractional shortening were significantly increased by Ex in female, but not male mice (p < 0.03 between FEx and FSd groups by Šidák's multiple comparisons testing). Left ventricular mass was not altered by Ex, but about 20% higher in M than F mice. Dual X-Ray Absorptiometry (DEXA) scanning revealed increased bone mineral content and density, in both sexes due to Ex, as well as, reduced body fat, but only in the F mice (p < 0.0001). Body fat was (%): 26.1 ± 0.4 (MSd); 26.1 ± 0.6 (MEx); 31.7 ± 1.8 (FSd); 20.8 ± 1.1 (FEx). Total lean mass was significantly higher in M, but not affected by Ex. Ex reduced final blood glucose (4-hour fasted, p = 0.0007 for Ex, mg/dl): 142 ± 5 (MSd); 128 ± 5 (MEx); 137 ± 4 (FSd); 117 ± 4 (FEx). Most fat pads (weighed at euthanasia) were reduced in mass in the F by Ex, but not necessarily in the M. Brown fat was increased by exercise in M, but reduced in F (g/40 g·bw): 0.34 ± 0.02 (MSd); 0.44 ± 0.03 (MEx); 0.37 ± 0.03 (FSd); 0.25 ± 0.04 (FEx), p = 0.0007 for interaction of exercise with sex (2-way ANOVA). Kidney, liver, and heart final wet weights were not affected by Ex, but lower in F (p < 0.0001 for sex for all 3). In conclusion, treadmill exercise to obese, aging TH M and F mice resulted in a several improved cardio-renal indices in addition to reducing weight, visceral fat mass, and increasing bone density. These studies support the prescription of vigorous cardiovascular exercise in aging, obese, insulin-resistant individuals. Funding to CE provided by the Marriott Foundation, the NIH CTSA Award pre-pilot, and internal Georgetown University sources This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.