March 26, 2025
BATON ROUGE – Scientists at Pennington Biomedical Research Center have gained greater clarity in the brain regions and neurons that control metabolism, body temperature and energy use. Featured in the February edition of the journal Metabolism, Dr. Heike Münzberg-Gruening and a team of researchers discovered which chemicals influence the signals that control how much energy the body uses. In " Leptin Receptor Neurons in the dorsomedial hypothalamus require distinct neuronal subsets for thermogenesis and weight loss ," researchers laid out the pathways, chemicals, neurons and brain regions that are activated.
In previous research, Dr. Münzberg-Gruening and her team identified that leptin receptors, or Lepr, control the metabolic effects of Leptin. These receptors are neurons in the dorsomedial hypothalamus, or DMH, which is a nucleus located in the hypothalamus at the base of the brain. In their latest study, researchers found that these Lepr neurons communicate using two different chemical signals: glutamate, which excites neurons, or GABA, which calms neurons.
The study revealed that the neurons that send signals to the brain region called the raphe pallidus - a region that controls metabolism - only use glutamate to send their signals. The neurons that signal to another brain region – the arcuate nucleus, which regulate body weight, satiety and metabolism – use only GABA. These neurons also have special receptors that allow them to respond to the new weight-loss medications known as GLP-1 receptor agonists.
"This discovery sheds light on the fundamental neuronal interplay that influences how much energy the body uses and how the body adjusts to changes in temperature levels or food availability," said Dr. Münzberg, professor in Pennington Biomedical's Central Leptin Signaling Lab. "This research expands our knowledge of the circuitry of thermoregulation and emphasizes the unique capability of leptin signaling in the DMH to promote beneficial metabolic effects. It also clarifies leptin signaling's role in the stability of body weight and energy usage. We believe these neurons manage the body's ability to adapt to a variety of environmental changes like ambient temperature or food scarcity by integrating signals like leptin and the gut hormone glucagon-like-peptide-1 or GLP-1."
In addition to identifying which neurons from the DMH affect certain regions and their functions, researchers further found that some Lepr neurons are muted by leptin, while others were activated specifically when certain indirect signals were blocked. This suggests that the DMH is part of a larger neuronal network and leptin increases the muting effect of outside connections with the DMH, but when these outside connections are blocked, leptin is able to un-mute DMH neurons. Such networks may be relevant to integrate and, if necessary, override environmental and humoral signals to allow proper adaptation of body energy balance.
This study further clarifies that Lepr neurons are a unique selection of DMH neurons that promote metabolic benefits. They might also explain the paradox that robust weight loss with GLP-1-based medications is able to override the slow metabolism usually associated with weight loss, but this paradox needs to be further tested in future studies.
"There are still so many fundamental processes in our bodies and brains that remain a mystery to us, and that's exactly what drives our researchers at Pennington Biomedical —to explore these unknowns, make new discoveries and deepen our understanding of metabolism," said Dr. John Kirwan, Executive Director of Pennington Biomedical Research Center. "I want to congratulate Dr. Münzberg and her team on this exciting discovery. It really showcases the incredible work that is happening in our Pre-Clinical Basic Science labs, and I can't wait to see what they'll discover next."
About the Pennington Biomedical Research Center
The Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the triggers of obesity, diabetes, cardiovascular disease, cancer and dementia. Pennington Biomedical has the vision to lead the world in promoting metabolic health and eliminating metabolic disease through scientific discoveries that create solutions from cells to society. The center conducts basic, clinical, and population research, and is a campus in the LSU System.
The research enterprise at Pennington Biomedical includes over 600 employees within a network of 44 clinics and research laboratories, and 13 highly specialized core service facilities. Its scientists and physician/scientists are supported by research trainees, lab technicians, nurses, dietitians, and other support personnel. Pennington Biomedical is a globally recognized state-of-the-art research institution in Baton Rouge, Louisiana.
