Fig. 1.

Metabolic response to WD feeding and CDN1163 treatment. Diagram of overall study design indicating experimental groups (A). After weaning, mice were placed on a standard chow diet. At 8 weeks of age, WT or Mc4r^−/− (KO) mice were either maintained on chow or switched to WD (±CDN1163) for another 8 weeks. One cohort of WT mice and one cohort of KO WD-fed mice were given CDN1163 injections once every 2 weeks (four in total) and one cohort of KO WD-fed mice was given CDN1163 injections three times a week (24 in total). All mice were 16 weeks of age upon completion of the study. mRNA expression of Serca2 (B). Data are presented as mean ± SEM (n ≥ 6). §P < 0.05 versus WT chow. Measurements of plasma free fatty acid levels (C), body weight (D), whole-body fat mass (E), average daily food intake (F), plasma insulin level (G), HOMA-IR (H), and glucose tolerance of WT (I) and KO (J) mice. Area under the curve (AUC) calculated from glucose tolerance test results (K). Data are presented as mean ± SEM (n ≥ 8). ∗P < 0.05 versus chow, #P < 0.05 versus WD. HOMA-IR, homeostatic model assessment for insulin resistance; SERCA, sarco/endoplasmic reticulum Ca²⁺-ATPase; WD, Western diet.