The Circadian Clock in the Ventromedial Hypothalamus Controls Cyclic Energy Expenditure

• Published in: Cell metabolism 2016-03, Vol.23 (3), p.467-478
• Main Authors: Orozco-Solis, Ricardo, Aguilar-Arnal, Lorena, Murakami, Mari, Peruquetti, Rita, Ramadori, Giorgio, Coppari, Roberto, Sassone-Corsi, Paolo
• Format: Article
• Language: English
• Subjects: Adipose Tissue, Brown - physiology; Adipose Tissue, White - physiology; Animals; ARNTL Transcription Factors - genetics; ARNTL Transcription Factors - metabolism; Circadian Clocks; Circadian Rhythm; Energy Metabolism; Homeostasis; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Transgenic; Neurons - metabolism; Period Circadian Proteins - physiology; Suprachiasmatic Nucleus - physiology; Sympathetic Nervous System - physiology; Thermogenesis
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2016.02.003

Organismal homeostasis relies on coherent interactions among tissues, specifically between brain-driven functions and peripheral metabolic organs. Hypothalamic circuits compute metabolic information to optimize energetic resources, but the role of the circadian clock in these pathways remains unclear. We have generated mice with targeted ablation of the core-clock gene Bmal1 within Sf1-neurons of the ventromedial hypothalamus (VMH). While this mutation does not affect the central clock in the suprachiasmatic nucleus (SCN), the VMH clock controls cyclic thermogenesis in brown adipose tissue (BAT), a tissue that governs energy balance by dissipating chemical energy as heat. VMH-driven control is exerted through increased adrenergic signaling within the sympathetic nervous system, without affecting the BAT’s endogenous clock. Moreover, we show that the VMH circadian clock computes light and feeding inputs to modulate basal energy expenditure. Thus, we reveal a previously unsuspected circuit where an SCN-independent, hypothalamic circadian clock controls BAT function, energy expenditure, and thermogenesis. [Display omitted] •BMAL1 in the VMH balances circadian BAT activity•BMAL1 in the VMH does not affect BAT’s endogenous clock•The clock in the VMH computes light and feeding inputs to modulate energy-expenditure Orozco-Solis et al. reveal that the circadian clock of the ventromedial hypothalamus controls circadian energy expenditure through the rhythmic activation of BAT’s metabolism and dissipating energy as heat. Furthermore, this SCN-independent clock can compute environmental zeitgebers, including light and feeding inputs, to balance circadian energy expenditure.