PMC

Experimental design for high fat diet meal feeding study. The diagram illustrates the feeding regimes used in the current study; early (EHF) and late (LHF) high fat diet meal feeding. Mice were fed either control or high fat diets in a time-of-day-dependent manner, as outlined in the figure and in the Methods. Feeding regimes were enforced for a 9 weeks period.

Impact of STZ-induced diabetes on whole body adaptation in mice. (A) i) Plasma insulin, ii) glucose, and iii) NEFA levels in STZ/Vehicle mice. Data shown as mean ± SEM for 6 mice/ZT/experimental group. (B) i) Body weight change. ii) body fat, iii) total caloric intake, and iv) physical activity (arbitrary units; A.U.). Data shown as mean ± SEM for 12 mice/experimental group in panel i, and 6 mice/experimental group in panels ii-iii. *, p<0.05 for WT vehicle versus WT STZ; #, p<0.05 for CCM vehicle versus CCM STZ.

Impact of high fat diet meal feeding on whole body adaptation in mice. (A) i) Fat caloric intake, ii) respiratory exchange ratio (RER), and iii) plasma NEFA levels. Data shown as mean ± SEM for 21 mice/experimental group in panels i-ii and 3 mice/ZT/experimental group in panel iii. *, p<0.05 for EHF vehicle LHF at ZT24. (B) i) Body weight change. ii) body fat, iii) total caloric intake, and iv) physical activity. Data shown as mean ± SEM for 6 mice/experimental group in panel ii and 21 mice/experimental group in panels iii-iv.

Differential metabolic adaptation of the heart to STZ-induced diabetes in WT versus CCM mice. (A) i) Substrate reliance, ii) Glucose oxidation reliance, iii) myocardial oxygen consumption, iv) ¹⁴C-lactate release rate, v) myocardial glycogen levels, and vi) myocardial triglyceride levels. Data shown as mean ± SEM for 6 mice/experimental group. *, p<0.05 for WT vehicle versus WT STZ. (B) i) Cte1 mRNA, ii) Cd36 mRNA, iii) Pdk4 mRNA, iv) Ucp3 mRNA, v) Mcad mRNA, vi) Mcd mRNA, vii) CTE1 protein levels at ZT6, and viii CTE1 protein levels at ZT18. Data shown as mean ± SEM for 6 mice/ZT/experimental group. *, p<0.05 for WT vehicle versus WT STZ; #, p<0.05 for CCM vehicle versus CCM STZ. (C) i) p-AMPK/t-AMPK at ZT6, ii) p-AMPK/t-AMPK at ZT18, iii) p-ACC/t-ACC at ZT6, and iv) p-ACC/t-ACC at ZT6. Data shown as mean ± SEM for 6 mice/experimental group. (D) i) Nampt mRNA, ii) NAMPT protein levels at ZT6, iii) NAMPT protein levels at ZT18, and iv) protein acetyl-lysine levels at ZT6. Data shown as mean ± SEM for 6 mice/ZT/experimental group.

Differential metabolic adaptation of the heart to high fat diet meal feeding in WT versus CCM mice. (A) i) Substrate reliance. ii) myocardial oxygen consumption, iii) ¹⁴C-lactate release rate, iv) myocardial glycogen levels, and v) myocardial triglyceride levels. Data shown as mean ± SEM for 6 mice/experimental group in panels i-iii and 12 mice/experimental group in panels iv-v. (B) i) Cte1 mRNA, ii) Cd36 mRNA, iii) Pdk4 mRNA, iv) Ucp3 mRNA, v) Mcad mRNA, and vi) Mcd mRNA. Data shown as mean ± SEM for 6 mice/ZT/experimental group. (C) i) p-AMPK/t-AMPK at ZT6, and ii) p-ACC/t-ACC at ZT6. Data shown as mean ± SEM for 6 mice/experimental group. (D) i) Nampt mRNA, ii) NAMPT protein at ZT6, and iii) protein acetyl-lysine levels at ZT6. Data shown as mean ± SEM for 6 mice/ZT/experimental group.