Differences in mitochondrial efficiency between lines of mice divergently selected for heat loss.

Divergent selection for heat loss was applied to lines of mice for 15 generations (G) in 3 replicates. Selection resumed at G42 and continued through G51 across all replicates. At the end of G51, differences in heat loss and feed intake per unit of BW were approximately 56 and 34%, respectively, between high heat loss (MH) and low heat loss (ML) lines, as a percentage of the control line (MC) mean. Rates of liver 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 maintenance requirements. Body composition, BW, liver weight, feed intake, and residual feed intake (RFI) were also measured or calculated. Results reported here represent data from 197 mature male mice from all replicates. There were no differences in BW (P = 0.91) between the selection lines. Selection had an effect on lean percentage (P = 0.02), with MH mice being leaner. Fat percentage differences between the selection lines tended toward significance (P = 0.13). Livers of MH mice were approximately 13% larger than livers of ML mice (P = 0.01). An effect of selection was observed (P < 0.01) in feed intake per unit BW, 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), whereas state 3 rates approached significance (P = 0.06). Mitochondria of MH mice respired at a greater rate than mitochondria of ML mice in all states of respiration; ML mice had respiratory control ratios that were, on average, 8% greater than MH mice (P = 0.14). Although this difference only tended toward significance, we suspect a greater degree of coupling of mitochondrial processes exists in ML animals. Mice selected for reduced heat loss had ADP:oxygen ratios that were approximately 20% greater than MH mice (P = 0.03). Therefore, greater mitochondrial efficiency was expressed in the ML animals. Within a line-replicate, there was no correlation between ADP:O and feed intake per unit BW (P = 0.71). In addition, no correlation of ADP:O and RFI existed (P = 0.92). Although the selection lines differed in mitochondrial traits, including overall mitochondrial efficiency (ADP:oxygen), these differences were not a significant underlying cause of variation in feed intake per unit BW or in RFI estimates.

Uncoupling proteins and energy expenditure in mice divergently selected for heat loss.

The objective of this study was to determine whether variation in energy expenditure created by selection on heat loss is mediated by uncoupling protein-1 (UCP1) in brown adipose tissue. Divergent selection for heat loss developed lines of mice with high (MH) and low (ML) maintenance energy expenditure. Concentration of UCP1 mRNA in brown adipose tissue (BAT) was 93% greater in ML than in MH mice (P < 0.02). Two new lines of mice, KH and KL, were bred by backcrossing a UCP1 knockout gene into the MH and ML lines, respectively; KH and KL with both knock-out (-/-) and wild type (+/+) UCP1 genotypes were generated. At 13 wk of age, KH mice exhibited greater heat loss (166 kcal x kg(0.75) x d(-1)) than KL mice (126.4 kcalkg(0.75) x d(-1)) regardless of the UCP1 knockout (P < 0.0001). Concentration of UCP2 mRNA in BAT was 74% greater in UCP1 knockout mice (-/-) than in wild type (+/+; P = 0.0001). We conclude that response to selection for increased energy expenditure was not mediated by increased expression or function of UCP1.