Nuclear receptor expression links the circadian clock to metabolism

Area of Science:

• Endocrinology
• Metabolism
• Chronobiology

Background:

• Nuclear receptors (NRs) are key sensors for hormones and lipids.
• Circadian rhythms regulate nutrient and energy metabolism.
• Understanding NR expression dynamics is crucial for metabolic health.

Purpose of the Study:

• To investigate the diurnal expression profiles of all mouse nuclear receptors.
• To determine the role of NR oscillations in circadian entrainment of metabolism.
• To identify novel roles for NRs in linking peripheral clocks to metabolic outputs.

Main Methods:

• Comprehensive survey of diurnal expression of 49 mouse nuclear receptors.
• Analysis of NR expression in white adipose tissue, brown adipose tissue, liver, and skeletal muscle.
• Correlation of NR expression patterns with target gene activity.

Main Results:

• Of 45 expressed NRs, 25 exhibited rhythmic cycling, and 3 showed a single transient pulse.
• Thyroid hormone receptors (TRalpha and beta) displayed dramatic cycling, challenging 'basal metabolism' concepts.
• Coordinated changes in NR expression and target genes explain cyclic lipid and glucose metabolism.

Conclusions:

• Dynamic and coordinated NR expression is central to circadian metabolic regulation.
• NRs play significant roles in coupling peripheral circadian clocks to metabolic processes.
• Findings suggest a reevaluation of 'basal metabolism' in light of rhythmic hormonal signaling.