Comprehensive Laboratory Animal Monitoring System (CLAMS) apparatus was used to measure O2 consumption and CO2 production by the four different mouse groups (backcrossed to C57BL/6JCrl) at age P28–29. a Circadian rhythm of respiratory exchange ratio. b Average 12-h respiratory exchange ratio of daytime and nighttime measurements. c Average 12-h energy expenditure estimated by indirect calorimetry for daytime and nighttime. The plotted values represent weight-normalized energy expenditure from ANCOVA model with genotype as a fixed factor and weight as a covariate. d Hepatic gene expression of a hepatocyte-derived mitochondrial stress-inducible endocrine factor, Fgf21. e Hepatic gene expression of Gdf15, a macrophage-secreted marker of mitochondrial dysfunction. Statistics: one-way ANOVA (b, d, e) or ANCOVA (c) followed by planned comparisons with Welch’s t statistics.