Integrating GABA and dopamine signals to control meal initiation

When you feel hungry, your brain takes the necessary steps to consume food. Many of these steps are not well known, but new research has been published in the journal. metabolism A study by researchers at Baylor College of Medicine and the University of Texas Health Science Center at Houston has uncovered brain circuits and chemical messengers that help regulate meal initiation and food intake. The findings have implications for the development of improved treatments to manage the global obesity epidemic.

“It is well known that serotonin, a neurotransmitter in the brain, can inhibit food intake. This discovery suggests that drugs that interact with serotonin or its receptors to control food consumption and obesity ,” said corresponding author Dr. Yong Shu. Pediatrics – Deputy Director of Nutrition and Basic Sciences USDA/ARS Pediatric Nutrition Research Center At Baylor. “However, some of these drugs have undesirable side effects and are currently not available to patients. To improve drug design, we need to better understand how the brain regulates food intake. It needs to be deeply understood.”

of Xu Laboratory They have been studying the role of serotonin in feeding control for quite some time. In this study, we focused on a little-known component of serotonin control of food intake. They looked for brain circuits and neurotransmitters that modulate the activity of serotonin-producing neurons, activating or suppressing them at the right times to reach a balanced food intake. “We asked how this system could be used to regulate feeding,” Xu said.

Serotonin is primarily synthesized by neurons in the dorsal raphe nucleus (DRN) of the midbrain. Serotonergic neurons in the DRN project to numerous brain regions, including the arcuate hypothalamus (ARH). The research team showed that the ARH circuit and two neurotransmitters, GABA and dopamine, play important roles in meal initiation.

“Studies using animal models have shown that when animals are hungry, serotonin-producing neurons in the DRN are suppressed by GABA and dopamine. This reduces serotonin levels in the brain and inhibits the initiation of meals. It becomes possible,” Schuh explained. “When an animal feeds and reaches satiety, the inhibitory signals in serotonin neurons decrease and more serotonin is produced to inhibit feeding via projections to the ARH.”

“The unique thing about this is that GABA and dopamine act synergistically. When both are present, serotonin neurons seem to be more inhibited than when only one of the neurotransmitters is present,” Xu he said.
This study is important because it advances our understanding of how the brain manages body weight and feeding, particularly the role of neurotransmitters in a specific phase of eating behavior: meal initiation. This knowledge could aid in the development of improved obesity drugs.

“Looking forward, we are interested in identifying signals that regulate other stages of feeding,” Xu said.

Other contributors to this work include Kristine M. Conde, Huey Zhong Wong, Shuzheng Fang, Yongxiang Li, Meng Yu, Yue Deng, Qingzhuo Liu, Xing Fang, Mengjie Wang, Yuhan Shi, Olivia Z. Ginnard, and Yuxue Yang. , Longlong Tu, Hesong Liu, Hailan Liu, Na ying, Jonathan C. Bean, Junying Han, Megan Authors E. Burt, Sanika V. Jossy, Yongjie Yang, Qingchun Tong, Benjamin R. Arenkiel, Chunmei Wang, and Yang He are affiliated with Baylor College of Medicine or the University of Texas Health Science Center at Houston.

This research was supported by USDA/CRIS (grants 51000-064-01S, 3092-51000-062-04(B)S), the National Institutes of Health (grants R01DK120858, F32DK134121, R01DK131446), and the American Heart Association (grants 23POST1030352) Supported by