(A) Normal food intake and (B) increased oxygen consumption in middle-aged Dgat1^−/− mice (n = 11-12/genotype). (C) Reduced body weight and (D) fat mass in Dgat1^−/− mice. Body weight was measured monthly in mice from the aging cohort (n = 30/genotype). Total body mass is expressed as fat and lean mass composition for young and middle-aged groups (n = 11-12/genotype). “Young” and “Middle-aged” refer to ages 3-4 months (mo) and 12-13 mo, respectively (*p < 0.05 vs. WT. ^#p <0.05 vs. same genotype, different age). (E) Reduced levels of triglycerides in heart and gastrocnemius from middle-aged (15 mo) female mice [*p < 0.05 vs. wild-type (WT); n = 8-13]. The inguinal fat pads from Dgat1^−/− mice have fewer F4/80-positive (F) total leukocytes and (G) macrophages. (*p < 0.05 vs. WT; n = 5). F4/80-positive cells were separated into two populations, dim and bright, predicted to be the recruited and the resident macrophages, respectively [35]. Values are reported ± SEM.

Survival curves for female wild-type and Dgat1^−/− mice (n=30 per genotype). Further analysis of the data is summarized in Table 1.

(A) Reduced serum IGF-1 levels in middle-aged Dgat1^−/− mice (p< 0.05; n= 9-10). (B) Similar serum insulin levels observed in young and middle-aged WT and Dgat1^−/− mice (n= 8-13). (C) Reduced fecundity in female Dgat1^−/− mice (*p<0.005; n= 11 litters/genotype). “Young” and “Middle-aged” refer to ages 3–4 mo and 14–16 mo, respectively. Values are reported ± SEM.

(A) Differentially expressed genes (fold>1.3, non-adjusted t-test p<0.05) in the livers of WT calorie restricted (WTCR) vs. WT ad libitum mice (WTAL) compared to Dgat1^−/− ad libitum (Dgat1^−/− AL) vs. WTAL. (B) Gene-expression profiles (vertical axis) and biological replicates (horizontal axis) are shown in the context of the HOPACH cluster map. Ordered root HOPACH clusters (C1-9) represent significantly up-regulated (red) or down-regulated (green) genes relative to WTAL (WTAL data excluded). Over-represented cluster Gene Ontology and pathway terms (GO-Elite) are shown for the top-ranking distinct processes based on a permuted p-value. Dgat1 and genes previously associated with CR are indicated by an arrow next to the location of the corresponding gene probe set in the cluster map.