DHA supplementation abolished resistance of weight gain in Elovl2−/− mice. Total PUFA composition of liver (A) and serum (B) of wild-type and Elovl2−/− animals fed standard chow diet followed by 2 weeks of high-fat diet (Chow/HF) or prefed for 2 weeks with DHA-enriched diet followed by 2 weeks of high-fat diet (DHA/HF). For the experimental overview, see supplementary Fig. I, and for the % mole composition of remaining fatty acids, see supplementary Tables VI and VII. Relative hepatic gene expression of SREBP-1c, FAS, and SCD1 (C) in wild-type and Elovl2−/− mice fed for 2 weeks with DHA-enriched diet followed by 2 weeks of high-fat diet (DHA/HF) relative to values in wild-type mice fed chow diet (dotted line). Relative levels of nSREBP-1c protein in wild-type and Elovl2−/− animals fed for 2 weeks with DHA-enriched diet followed by 2 weeks of high-fat diet (DHA/HF) relative to values in wild-type mice fed chow diet (dotted line) (D). Increase in body weight of wild-type and Elovl2−/− animals fed standard chow diet followed by 2 weeks of high-fat diet (Chow/HF) or prefed for 2 weeks with DHA-enriched diet followed by 2 weeks of high-fat diet (DHA/HF), presented as mean of delta values after third week of treatment (E). Fat content in wild-type and Elovl2−/− animals measured at two time points: after 2 weeks prefed with standard chow diet (Chow) or DHA-enriched diet (DHA) followed by 2 weeks of high-fat diet (Chow/HF and DHA/HF), respectively (F). Relative hepatic gene expression of PPARγ (G) and Pck1 (H) in wild-type and Elovl2−/− mice fed standard chow diet (Chow), standard chow diet followed by 2 weeks of high-fat diet (Chow/HF), or 2 weeks with DHA-enriched diet followed by 2 weeks of high-fat diet (DHA/HF) relative to values in mice fed chow diet. Results shown are means ± SEM of 3–5 mice. Statistical significances are shown between wild-type and Elovl2−/− mice, as well as different diets (* P < 0.05, ** P < 0.01, *** P < 0.001, and **** P < 0.0001) and versus control values (mice fed chow diet) (# P < 0.05, ## P < 0.01 and ### P < 0.001, #### P < 0.0001).