Winda Ariyani1†, Chiharu Yoshikawa1†, Haruka Tsuneoka1†, Izuki Amano2, Itaru Imayoshi3,4,5, Hiroshi Ichinose6, Chiho Sumi-Ichinose7, Noriyuki Koibuchi2, Tadahiro Kitamura1, Daisuke Kohno1* (1．Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, Gunma, Japan, 2. Department of Integrative Physiology, Gunma University Graduate School of Medicine, Gunma, Japan, 3 Center for Living Systems Information Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan, 4 Department of Brain Development and Regeneration, Graduate School of Biostudies, Kyoto University, Kyoto, Japan, 5 Laboratory of Deconstruction of Stem Cells, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan, 6 School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan, 7 Department of Pharmacology, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan. †co-first author、*corresponding author)
About
Feeding behavior is controlled by various neural networks in the brain that are involved in different feeding phases: Food procurement, consumption, and termination. However, the specific neural circuits controlling the food consumption phase remain poorly understood. Here, we investigated the roles of dopaminergic neurons in the paraventricular nucleus of the hypothalamus (PVH) in the feeding behavior in mice. Our results indicated that the PVH dopaminergic neurons were critical for extending the food consumption phase and involved in the development of obesity through epigenetic mechanisms. These neurons synchronized with proopiomelanocortin neurons during consumption, were stimulated by proopiomelanocortin activation, and projected to the lateral habenula (LHb), where dopamine receptor D2 was involved in the increase in food consumption. In addition, upregulated tyrosine hydroxylase (TH) expression in PVH was associated with obesity and indispensable for obesity induction in mice lacking Dnmt3a. Taken together, our results highlight the roles of PVH dopaminergic neurons in promoting food consumption and obesity induction.
Paper information
Ariyani W, Yoshikawa C, Tsuneoka H, Amano I, Imayoshi I, Ichinose H, Sumi-Ichinose C, Koibuchi N, Kitamura T, Kohno D. Proc Natl Acad Sci U S A. 2025 Apr;122(13):e2411069122
Online URL
https://doi.org/10.1073/pnas.2411069122
