The Journal of neuroscience : the official journal of the Society for NeuroscienceMar 26, 2024

Removing the Bmal2 Gene Changes Brain Clocks That Control Daily Eating and Energy Balance

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Mar 30, 2026

Abstract

B2KO mice displayed 1.5-fold higher adiposity and fourfold higher fasted hyperinsulinemia compared to wild-type mice.

B2KO mice showed a shorter free-running circadian period (-14 min/cycle) compared to wild-type controls.
Daily rhythmicity in the expression of metabolic regulators was lost in B2KO mice.
The circadian window of eating was longer in B2KO mice, indicating altered feeding patterns.
Control mice exhibited bimodal patterns of food intake and meal numbers, which were absent in B2KO mice.
Food-anticipatory activity in response to restricted feeding was nearly abolished in B2KO mice.
Downregulation of genes coding for appetite-stimulating neuropeptides was observed in the mediobasal hypothalamus of B2KO mice.

Simplified

BMAL2 (ARNTL2) is a paralog of BMAL1 that can form heterodimers with the other circadian factors CLOCK and NPAS2 to activate transcription of clock and clock-controlled genes. To assess a possible role ofin the circadian regulation of metabolism, we investigated daily variations of energy metabolism, feeding behavior, and locomotor behavior, as well as ability to anticipate restricted food access in male mice knock-out for(B2KO). While their amount of food intake and locomotor activity were normal compared with wild-type mice, B2KO mice displayed increased adiposity (1.5-fold higher) and fasted hyperinsulinemia (fourfold higher) and tended to have lower energy expenditure at night. Impairment of the master clock in the suprachiasmatic nuclei was evidenced by the shorter free-running period (-14 min/cycle) of B2KO mice compared with wild-type controls and by a loss of daily rhythmicity in expression of intracellular metabolic regulators (e.g.,and). The circadian window of eating was longer in B2KO mice. The circadian patterns of food intake and meal numbers were bimodal in control mice but not in B2KO mice. In response to restricted feeding, food-anticipatory activity was almost prevented in B2KO mice, suggesting altered food clock that controls anticipation of food availability. In the mediobasal hypothalamus of B2KO mice, expression of genes coding orexigenic neuropeptides (includingand) was downregulated, whileexpression lost its rhythmicity. Together, these data highlight that BMAL2 has major impacts on brain regulation of metabolic rhythms, sleep-wake cycle, and food anticipation. Bmal2Bmal2Lipoprotein lipase Uncoupling protein 2Neuropeptide y Agouti-Related Peptide Lipoprotein lipase

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Removing the Bmal2 Gene Changes Brain Clocks That Control Daily Eating and Energy Balance

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