Eating for hunger or pleasure? This is how the brain handles these feeding behaviors
Many times we eat, not because we are hungry, but because of social pressures or food that is so appetizing, that, even though we are full, we just want another bite. Overeating, whether it is guided by hunger or pleasure, typically leads to obesity, which affects about 42% of the adults in the U.S., according to the Centers for Disease Control and Prevention.
Looking to contribute to the development of effective treatments for obesity, the lab of Dr. Yong Xu at Baylor College of Medicine together with an international team of researchers investigated in an animal model how the brain regulates feeding triggered by hunger or other factors.
Mapping the roads that control feeding behavior in the brain
Xu and his colleagues identified two distinct brain circuits formed by serotonin-producing neurons in the mouse midbrain. One of the circuits extends to the hypothalamus, while the other projects into another region of the midbrain. These circuits play very distinct roles in regulating feeding.
“We discovered that the circuit that projects to the hypothalamus primarily regulates hunger-driven feeding, but does not influence the non-hunger driven feeding behavior,” said Xu, professor of pediatrics – nutrition and molecular and cellular biology at Baylor. “The other circuit that projects into the midbrain regulates primarily the non-hunger driven feeding, but not the feeding behavior triggered by hunger.
This indicates that, at the circuit level, the brain wires the two types of feeding behavior differently.”
The other significant contribution of this work refers to the identification of potential molecular targets associated with the circuits that could be used to treat overeating.
“One potential target is serotonin receptors, which are molecules that mediate the functions of the neurotransmitter serotonin produced by the neurons,” Xu explained. “We found that two receptors, serotonin 2C receptor and serotonin 1B receptor, are involved in both types of feeding behavior. Our data suggests that combining compounds directed at both receptors might produce a synergistic benefit by suppressing feeding.”
In addition, the team identified ion channels associated with the circuits that also might offer an opportunity to regulate the feeding behaviors. “One is the GABA A receptor, a chloride channel, found to be important in regulating serotonin circuits during hunger-driven feeding, but not during non-hunger driven feeding,” Xu said.
The other is a potassium channel that influences feeding triggered by hunger-independent cues, but not hunger-driven feeding.
There is a clear segregation of these two ion channels,” Xu said. “They have distinct functions in feeding behavior, which suggests they also could be target candidates to regulate overeating.”
The findings have encouraged the researchers to conduct future studies to identify more molecules that could modulate the activity of the ion channels to produce anti-overeating effects in animal models. “We also want to explore how external factors related to nutrition might affect ion channel functions at the molecular level,” Xu said.
Read the complete work in the journal Molecular Psychiatry.
The following authors also contributed to this work: Yanlin He, Xing Cai, Hailan Liu, Kristine M. Conde, Pingwen Xu, Yongxiang Li, Chunmei Wang, Meng Yu, Yang He, Hesong Liu, Chen Liang, Tingting Yang, Yongjie Yang, Kaifan Yu, Julia Wang, Rong Zheng, Feng Liu, Zheng Sun, Lora Heisler, Qi Wu, Qingchun Tong, Canjun Zhu and Gang Shu. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, South China Agricultural University, University of Texas Health at San Antonio, University of Aberdeen and University of Texas Health Science Center at Houston.
The investigators were supported by grants from the NIH (R01DK114279, R01DK109934, R21NS108091, R01ES027544, R01DK111436, R00DK107008, R01DK109194, R56DK109194, P01DK113954, R01DK115761, R01DK117281, R01DK125480, R01DK120858, K01DK119471 and P20GM135002).
Further support was provided by USDA/CRIS (51000-064-01 S), American Diabetes Association (1-17-PDF-138, 7-13-JF-61 and 1-15-BS-184), American Heart Association awards (16POST27260254), the Pew Charitable Trust awards (0026188), Baylor Collaborative Faculty Research Investment Program grants, the Faculty Start-up grants from USDA/ARS, the Biotechnology and Biological Sciences Research Council (BB/K001418/1 and BB/NO17838/1), the Medical Research Council (MC/PC/15077), a Pew Scholarship of Biomedical Sciences and a Kavli Scholarship.
