Time-Restricted Feeding Prevents Obesity and Metabolic Syndrome in Mice Lacking a Circadian Clock

Area of Science:

• Chronobiology
• Metabolic Physiology
• Molecular Biology

Background:

• Circadian clock disruption is linked to metabolic diseases.
• Mutant mice often lack normal feeding-fasting cycles, confounding previous studies.
• The necessity of a molecular clock for metabolic homeostasis is debated.

Purpose of the Study:

• To investigate if time-restricted feeding (TRF) can prevent metabolic diseases in mice with disrupted circadian clocks.
• To assess the impact of TRF on obesity and metabolic syndrome in specific knockout mouse models.
• To understand the role of circadian rhythms in maintaining metabolic balance.

Main Methods:

• Utilized whole-body Cry1;Cry2 and liver-specific Bmal1 and Rev-erbα/β knockout mice.
• Compared metabolic outcomes under ad libitum feeding versus TRF (10-hour dark phase access).
• Performed transcriptome and metabolome analyses to examine molecular and metabolic changes.

Main Results:

• Mice rapidly gained weight and exhibited metabolic defects with ad libitum feeding.
• TRF protected mice from excessive weight gain and metabolic diseases, irrespective of genotype.
• TRF reduced hepatic lipid accumulation and enhanced cellular defenses against metabolic stress.

Conclusions:

• Circadian rhythms are crucial for maintaining metabolic homeostasis.
• Daily feeding and fasting rhythms, regulated by the circadian clock, are essential for preventing metabolic diseases.
• TRF can mitigate metabolic dysfunction by restoring rhythmic feeding patterns and balancing nutrient/stress responses.