Mitochondrial efficiency in lines of mice divergently selected for heat loss

Divergent selection for heat loss was applied to lines of mice for 15 generations (G) in three replicates. Selection resumed at G42 and continued through G51 across all replicates. Selection of this sort resulted in differences of 55.7% and 34% in heat loss and feed intake, respectively, at the end of G51 between high heat loss (MH) and low heat loss (ML) lines. Rates of mitochondrial respiration states, degree of coupling and mitochondrial efficiency were measured in G58 using a Clark-type oxygen electrode to investigate possible causes of underlying variation in feed intake. Body weight, body composition, liver weight, and feed intake were also measured. Results reported here represent data from 197 mature male mice from replicates 1, 2 and 3. There were no significant differences in body weights (P=0.91) between the selection lines. Selection had a significant effect on percent lean tissue (P=0.02) with MH mice being leaner, while differences in percent fat between the lines approached significance (P=0.13) with ML mice being fatter. Livers of MH mice were approximately 13% larger than for ML mice (P=0.01). An effect of selection was observed (P\u3c0.01) in feed intake/body weight with MH mice consuming 29% more feed than ML mice in G58. Differences in State 2 and State 4 respiration rates were significant (P=0.01), while State 3 rates approached significance (P=0.06); mitochondria of MH mice respired faster than in ML mice. ML mice had respiratory control ratios that were, on average, 8% greater than MH mice (P=0.14), suggesting a greater degree of coupling in ML animals. ML mice had ADP:O ratios that were approximately 20% greater than MH mice (P=0.03). Therefore, greater mitochondrial efficiency is expressed in the ML animals. Across all replicates a partial correlation of -0.33 was observed between feed/body weight and ADP:O. However, within a line-replicate this correlation failed to exist. Even though lines differed in ADP:O, it was difficult to detect any part of this difference explaining line differences in feed intake