Dopaminergic neurons in the paraventricular hypothalamus extend the food consumption phase

Proc Natl Acad Sci U S A. 2025 Apr;122(13):e2411069122. doi: 10.1073/pnas.2411069122. Epub 2025 Mar 28.

Abstract

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.

Keywords: DNA methylation; dopamine; food intake; hypothalamus.

MeSH terms

  • Animals
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methyltransferase 3A
  • Dopaminergic Neurons* / metabolism
  • Dopaminergic Neurons* / physiology
  • Eating* / physiology
  • Epigenesis, Genetic
  • Feeding Behavior* / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / physiopathology
  • Paraventricular Hypothalamic Nucleus* / cytology
  • Paraventricular Hypothalamic Nucleus* / metabolism
  • Paraventricular Hypothalamic Nucleus* / physiology
  • Pro-Opiomelanocortin / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Tyrosine 3-Monooxygenase
  • DNA Methyltransferase 3A
  • Dnmt3a protein, mouse
  • Receptors, Dopamine D2
  • DNA (Cytosine-5-)-Methyltransferases
  • Pro-Opiomelanocortin