Sexual dimorphism of circadian liver transcriptome.

Sexual dimorphism affects various aspects of physiology, metabolism and longevity. Circadian clock is a master regulator of metabolism. Anti-aging dietary interventions reprogram circadian transcriptome in the liver and other tissues, but little is known about sexual dimorphism of circadian transcriptome.

Circadian clock controls rhythms in ketogenesis by interfering with PPARα transcriptional network.

Ketone bodies are energy-rich metabolites and signaling molecules whose production is mainly regulated by diet. Caloric restriction (CR) is a dietary intervention that improves metabolism and extends longevity across the taxa. We found that CR induced high-amplitude daily rhythms in blood ketone bodies (beta-hydroxybutyrate [βOHB]) that correlated with liver βOHB level.

Circadian Control of Mitochondria in Reactive Oxygen Species Homeostasis.

Mitochondria produce most of the cellular ATP through the process of oxidative phosphorylation. Energy metabolism in the mitochondria is associated with the production of reactive oxygen species (ROS). Excessive ROS production leads to oxidative stress and compromises cellular physiology.

Two-meal caloric restriction induces 12-hour rhythms and improves glucose homeostasis.

Glucose metabolism is tightly regulated and disrupting glucose homeostasis is a hallmark of many diseases. Caloric restriction (CR), periodic fasting, and circadian rhythms are interlinked with glucose metabolism. Here, we directly investigated if CR depends on periodic fasting and circadian rhythms to improve glucose metabolism.

CR reprograms acetyl-CoA metabolism and induces long-chain acyl-CoA dehydrogenase and CrAT expression.

Calorie restriction (CR), an age delaying diet, affects fat oxidation through poorly understood mechanisms. We investigated the effect of CR on fat metabolism gene expression and intermediate metabolites of fatty acid oxidation in the liver. We found that CR changed the liver acylcarnitine profile: acetylcarnitine, short-chain acylcarnitines, and long-chain 3-hydroxy-acylcarnitines increased, and several long-chain acylcarnitines decreased.

Reduced caloric intake and periodic fasting independently contribute to metabolic effects of caloric restriction.

Caloric restriction (CR) has positive effects on health and longevity. CR in mammals implements time-restricted (TR) feeding, a short period of feeding followed by prolonged fasting. Periodic fasting, in the form of TR or mealtime, improves metabolism without reduction in caloric intake.