Intrinsic cardiorespiratory fitness modulates clinical and molecular response to caloric restriction

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

“…Importantly, HCR and LCR also exhibit differences in nutrient handling and whole-body substrate preference [ 13 ] that suggest increased metabolic flexibility and fatty acid (FA) oxidative capacity in the HCR rat. Concordantly, gene and protein expression studies in the heart and muscle indicate that compared to LCR, HCR are enriched for genes related to FA metabolism and the mitochondrial respiratory chain [ [14] , [15] , [16] , [17] ]. The HCR and LCR rat lines provide an excellent model to better understand how individuals with higher or lower intrinsic metabolic risk metabolize substrates differently at the level of the mitochondria.…”

“…Indirect calorimetry studies indicate that HCR have increased resting oxygen consumption compared to LCR [ 16 , [18] , [19] , [20] , [21] ]. During exercise, the whole-body ratio of FA to carbohydrate oxidation levels tend to be higher in HCR than in LCR, which may be the primary mechanism by which the HCR can run for extended time periods during a VO 2 max test compared to LCR [ 13 ].…”