Unveiling leptin signaling in the DMH for metabolic effects

Scientists from Pennington Biomedical Research Center have been given more clarity in the brain areas and neurons that control metabolism, body temperature and energy consumption. Published in the February edition of the magazine MetabolismDr. Heike Münzberg-Gruene and a team of researchers discovered which chemicals influence the signals that determine how much energy the body uses. In “Leptin receptor drivers in the dorsomedial hypothalamus, different neuronal subsets require thermogenesis and weight loss,” researchers explained the paths, chemicals, neurons and brain areas that are activated.

In earlier research, Dr. Münzberg-Grusening and her team that leptin receptors, or Lepr, control the metabolic effects of leptin. These receptors are neurons in the dorsomedial hypothalamus, or DMH, some core in the hypothalamus at the base of the brain. In their latest study, researchers discovered that these Lepr neurons communicate with the help of two different chemical signals: glutamate, which fascinates neurons, or Gaba, which soothes neurons.

The study showed that the neurons that send signals to the brain area called the Raphe Pallidus – an area that controls metabolism – only use glutamate to send their signals. The neurons that identify with another brain area – the arc -shaped core, which regulate body weight, saturation and metabolism – only use GABA. These neurons also have special receptors with which they can respond to the new weight loss medicines 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 adapts to changes in temperature levels or food availability,” Dr. Münzberg, professor in the central leptin signal lab of Pennington Biomedical.

This research expands our knowledge of the circuit of thermoregulation and emphasizes the unique capacity of leptin signaling in the DMH to promote favorable metabolic effects. It also clarifies the role of leptins signaling in the stability of body weight and energy consumption. We believe that these neurons manage the body’s ability to adapt to a variety of changes in the environment, such as ambient temperature or food scarcity by integrating signals such as leptin and the intestinal hormone glucagon-like peptide-1 or GLP-1. “

Dr. Heike Münzberg-Gruene, Pennington Biomedical Research Center

In addition to identifying which neurons of the DMH influence certain regions and their functions, researchers further found that some Lepr neurons are filled in by leptin, while others were specifically activated when certain indirect signals were blocked. This suggests that the DMH is part of a larger neuronal network and leptin increases the damping effect of external connections with the DMH, but when these external connections are blocked, leptin is able to make non-mute DMH neurons. Such networks can be relevant to integrate and, if necessary, to ignore environmental and humoral signals to make a good adjustment of the body energy balance possible.

This study further clarifies that Lepr neurons are a unique selection of DMH neurons that promote metabolic benefits. They can also explain the paradox that robust weight loss with GLP-1-based medicines is able to ignore slow metabolism that is usually associated with weight loss, but this paradox must be further tested in future studies.

“There are still so many fundamental processes in our body and brain that remain a mystery to us, and that is exactly what our researchers drives at Pennington Biomedical -to explore these strangers, make new discoveries and to deepen our understanding of metabolism,” 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 shows the incredible work that happens in our pre-clinical basic science laboratories, and I can’t wait to see what they will discover below.”