Circadian Clocks and Feeding Time Regulate the Oscillations and Levels of Hepatic Triglycerides

• Lipidomic analysis reveals circadian oscillations in hepatic triglyceride levels
• Circadian oscillations in hepatic triglycerides persist in clock-disrupted mice
• PPARs and triglyceride enzymes are circadianly expressed in clock-disrupted mice
• Feeding time regulates the phase and levels of hepatic triglyceride accumulation

SummaryCircadian clocks play a major role in orchestrating daily physiology, and their disruption can evoke metabolic diseases such as fatty liver and obesity. To study the role of circadian clocks in lipid homeostasis, we performed an extensive lipidomic analysis of liver tissues from wild-type and clock-disrupted mice either fed ad libitum or night fed. To our surprise, a similar fraction of lipids (∼17%) oscillated in both mouse strains, most notably triglycerides, but with completely different phases. Moreover, several master lipid regulators (e.g., PPARα) and enzymes involved in triglyceride metabolism retained their circadian expression in clock-disrupted mice. Nighttime restricted feeding shifted the phase of triglyceride accumulation and resulted in ∼50% decrease in hepatic triglyceride levels in wild-type mice. Our findings suggest that circadian clocks and feeding time dictate the phase and levels of hepatic triglyceride accumulation; however, oscillations in triglycerides can persist in the absence of a functional clock.

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