Scientists at the Pennington Biomedical Research Center have gained deeper insight into the brain regions and neurons that regulate metabolism, body temperature, and energy expenditure. In a study published in the February edition of Metabolism, Dr. Heike Münzberg-Gruening and her research team identified the chemical signals that influence how the body manages energy.

Their study, "Leptin Receptor Neurons in the Dorsomedial Hypothalamus Require Distinct Neuronal Subsets for Thermogenesis and Weight Loss," outlines the pathways, neurotransmitters, and brain regions involved in these processes.

Previous research by Dr. Münzberg-Gruening’s team revealed that leptin receptors (Lepr) in the dorsomedial hypothalamus (DMH) regulate the metabolic effects of leptin. In this latest study, the researchers found that Lepr neurons communicate using two different neurotransmitters: glutamate, which excites neurons, and GABA, which inhibits them.

Key findings include:

• Lepr neurons signaling to the raphe pallidus—a brain region controlling metabolism—exclusively use glutamate.

• Lepr neurons signaling to the arcuate nucleus—which regulates body weight, satiety, and metabolism—only use GABA.

• These neurons also respond to GLP-1 receptor agonists, a class of weight-loss medications.

“This discovery enhances our understanding of how the brain regulates energy use, temperature adaptation, and responses to food availability,” said Dr. Münzberg, a professor at Pennington Biomedical’s Central Leptin Signaling Lab. “Our findings clarify leptin’s role in body weight stability and metabolism and highlight how these neurons help the body adapt to environmental changes like temperature shifts and food scarcity.”

Further, the researchers found that while some Lepr neurons are suppressed by leptin, others are activated when certain indirect signals are blocked, indicating that the DMH operates within a broader neuronal network. This suggests that leptin plays a role in muting external signals, and when those connections are inhibited, leptin can directly activate DMH neurons. Such networks may help integrate and override environmental and hormonal signals to maintain energy balance.

The study also sheds light on how Lepr neurons uniquely support metabolic health and may explain why GLP-1-based medications effectively promote weight loss despite the slower metabolism typically associated with weight reduction. However, further research is needed to explore this paradox.

“There is still so much we don’t understand about the fundamental processes regulating metabolism,” said Dr. John Kirwan, Executive Director of Pennington Biomedical Research Center. “Dr. Münzberg and her team’s groundbreaking work exemplifies the innovative research happening in our Pre-Clinical Basic Science labs, and I look forward to seeing what they uncover next.”

Source: https://www.pbrc.edu/news/media/2025/leptin-receptors-and-body-temperature-regulation.aspx