Epac2a-KO mice display an enhanced response to the cold challenge. Changes in the body temperature (A, n = 9) and fat weight (B, n = 8) during a 6 h exposure to cold (4°C). Protein and mRNA expression of thermogenic markers (C and D, n = 4) and mRNA expression of fatty acid oxidation markers (E, n = 8) in the iBAT of WT and KO mice. (F) Changes in the body temperature of WT mice with or without leptin administration during a 6 h exposure to cold (4°C). WT mice in the leptin group were injected i.p. with leptin (5 μg/g) before cold exposure, whereas WT mice in the control group were injected i.p. with the same volume of PBS (n = 8). *P < 0.05, **P < 0.01, and ***P < 0.001 compared to WT_25°C. #P < 0.05, ##P < 0.01, and ###P < 0.001 compared to WT_4°C without any treatment. Data represent the mean ± SEM. Sub: subcutaneous fat; Epi: epididymal fat; Lep: leptin.