Circadian regulation of hedonic appetite in mice by clocks in dopaminergic neurons of the VTA

• Published in: Nature communications Vol. 11; no. 1; p. 3071
• Main Authors: Koch, C. E., Begemann, K., Kiehn, J. T., Griewahn, L., Mauer, J., M. E. Hess, Moser, A., Schmid, S. M., Brüning, J. C., Oster, H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.06.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 38/39; 38/61; 631/378/1385/2640; 631/443/319/1488; 64/60; 96/44; Animals; Appetite; Behavior, Animal; Biological clocks; Choice Behavior; Circadian Rhythm; Circadian rhythms; Diet; Dopamine receptors; Dopaminergic Neurons - physiology; Feeding Behavior; Food; Food intake; Homeostasis; Humanities and Social Sciences; Male; Metabolic disorders; Metabolism; Mice; Mice, Inbred C57BL; multidisciplinary; Neurons; Obesity - metabolism; Oscillometry; Place preference conditioning; Science; Science (multidisciplinary); Ventral Tegmental Area - physiology; Ventral tegmentum
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16882-6

Unlimited access to calorie-dense, palatable food is a hallmark of Western societies and substantially contributes to the worldwide rise of metabolic disorders. In addition to promoting overconsumption, palatable diets dampen daily intake patterns, further augmenting metabolic disruption. We developed a paradigm to reveal differential timing in the regulation of food intake behavior in mice. While homeostatic intake peaks in the active phase, conditioned place preference and choice experiments show an increased sensitivity to overeating on palatable food during the rest phase. This hedonic appetite rhythm is driven by endogenous circadian clocks in dopaminergic neurons of the ventral tegmental area (VTA). Mice with disrupted clock function in the VTA lose their hedonic overconsumption rhythms without affecting homeostatic intake. These findings assign a functional role of VTA clocks in modulating palatable feeding behaviors and identify a potential therapeutic route to counteract hyperphagy in an obesogenic environment. In addition to promoting overconsumption, palatable diets dampen daily intake patterns, which further augments metabolic dysfunction. Here, the authors find that in mice, circadian clocks in dopaminergic neurons in the ventral tegmental area drive hedonic appetite rhythms.