Genetically determined exercise capacity affects systemic glucose response to insulin in rats

Abstract

Introduction: Aerobic exercise capacity is inversely related to morbidity and mortality as well as to insulin resistance. However, exercising in patients has led to conflicting results, presumably because aerobic exercise capacity consists of intrinsic (genetically determined) and extrinsic (environmentally determined) parts. The contribution of both parts to insulin sensitivity is also not clear. We investigated sedentary and exercised (aerobic interval training) high (HCR) and low capacity runners (LCR) differing in their genetically determined aerobic exercise capacity to determine the contribution of both parts to insulin sensitivity. Methods and Results: LCR and HCR differed in their untrained exercise capacity and body weight. Sedentary LCR displayed a diabetic phenotype with higher random glucose, lower glucose infusion rate during hyperinsulinemic euglycemic clamping than HCR. Echocardiography showed equal morphological and functional parameters and no change with exercise. Four weeks of exercise caused significant improvements in aerobic exercise capacity, which was more pronounced in LCR. However, with respect to glucose use, exercise affected HCR only. In these animals, exercise increased 2-deoxyglucose uptake in gastrocnemius (+58.5 %, p= 0.1) and in epididymal fat (+106 %; p<0.05). Citrate synthase activity also increased in these tissues (gastrocnemius 69 % epididymal fat 63 %). Conclusion: In our model of HCR and LCR, genetic predisposition for low exercise capacity is associated with impaired insulin sensitivity and impedes exercise-induced improvements in insulin response. Our results suggest that genetic predisposition for low aerobic exercise capacity impairs insulin response, which may not be overcome by exercise.

Lactate thresholds and role of nitric oxide in male rats performing a test with forced swimming to exhaustion

“…Despite all of the rats being of the same age, being housed in the same conditions, being fed the same diet, and having no previous training, some rats showed higher inborn physical endurance. These results are fully consistent with the hypothesis that genetics is an important determinant of the response to physical activity (Koch et al, 2005) and may affect the features of anatomy (Britton & Koch, 2001), pulmonary function (Kirkton et al, 2009), insulin response (Schwarzer et al, 2021), and the predominant type of skeletal muscle fibers (Abernethy et al, 1990). It was expected that the metabolism in rats with different physical endurance would be different.…”

Exercise Training Differentially Affects Skeletal Muscle Mitochondria in Rats with Inherited High or Low Exercise Capacity

“…These findings further indicate that several effects of exercise depend on intrinsic exercise capacity. In male rats, it has been shown by us that exercise training affects deoxyglucose uptake and citrate synthase activity in several tissues in HCR but not in LCR [ 25 ]. Similarly, results from investigations in humans indicate that exercise training in genetically predisposed populations seems to be frequently ineffective as has been shown for African, Arabic, Chinese, or Polynesian subjects [ 69 ].…”

“…For cohort 2, rats from generation 36 had been trained (HCR n = 9, LCR n = 11; completion of the exercise training: HCR n = 6, LCR n = 10; sedentary rats: HCR n = 8, LCR n = 8). Exercise was performed as aerobic interval training (AIT) for 105 min/day, 5 days/week, 4 weeks in total, on a treadmill at a 25° incline as described elsewhere [ 25 ]. Two treadmills were used in parallel, allowing a total of 6 rats to be trained.…”

Higher mitochondrial oxidative capacity is the primary molecular differentiator in muscle of rats with high and low intrinsic cardiorespiratory fitness

“…Although CS activity has been consistently reported as higher in HCR compared to LCR skeletal muscle [ 23 , 24 , 27 , 28 ], markers of mitochondrial biogenesis do not differ between lines. While intrinsic fitness in humans is associated with longevity, independent of exercise training or other metabolic risk factors [ 5 ], studies observing the intersection of life-long physical activity and muscle gene expression have linked exercise with the upregulation of pathways related to energy handling and mitochondrial biogenesis [ 52 ].…”

“…Computational modeling of this dataset predicted that the preferential glucose utilization in LCR is due to both lower mitochondrial density as well as lower activity of FA transport enzymes [ 22 ]. This model has been supported by repeated evidence of increased mitochondrial density in the skeletal muscle of HCR versus LCR [ [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] ], although studies in the myocardium show equivalent levels of CS activity and mitochondrial complex proteins in HCR and LCR animals, suggesting comparable mitochondrial densities [ 18 , 23 , 33 ]. While increased mitochondrial density in the HCR skeletal muscle has been demonstrated, no study has directly addressed whether the increased respiration capacity in the HCR is a function of increased density alone, or whether there are intrinsic differences in the HCR mitochondria independent of mass differences.…”