According to a new study by researchers at the Yale School of Medicine, a set of neurons closely associated with female lactation may also play an important role in regulating hunger and body weight.
The study, published in the journal Nature Neuroscience on Aug. 22, was conducted by professor of neurosurgery Anthony Van den Pol GRD ’77 and associate research scientist Xiaobing Zhang. The scientific community has long known that the area of the brain called the arcuate nucleus of the hypothalamus plays a key role in regulating human metabolism. Prior research has revealed that within the arcuate nucleus, a set of cells known as pro-opiomelanocortin neurons play an especially significant role in controlling food intake.
However, research into the role of cells surrounding POMC neurons has been relatively sparse. Van den Pol and Zhang’s study is one of the first to examine the role of neighboring cells known as tyrosine hydroxylase, or TH, neurons, which have largely been associated with lactation in women. The researchers used optogenetics, a biological technique that involves the use of light to control living tissue, to selectively activate the TH nerve cells in living mice. When the cells were activated, the mice began to eat, but when the researchers stopped stimulating the cells, the mice stopped eating. The study authors said their results are important for understanding metabolic factors that contribute to obesity and eating disorders.
“The main finding of our study was that TH neurons in the arcuate nucleus have a new function, which was not known of before,” Zhang said. “That function allows TH neurons to regulate food intake and body weight.”
Additionally, the researchers found that TH neurons release transmitters that can inhibit other neurons that control food intake, including POMC neurons. Van den Pol and Zhang also discovered that ghrelin, a hormone found in the gut and often referred to as the “hunger hormone,” can travel to the brain and excite the TH nerve cells and induce increased eating.
While the study offers important new insights into the neurobiology of metabolism, the research was not seamless. According to Zhang, the researchers encountered significant hurdles while conducting the study. Zhang pointed out, for instance, that the process of activating the TH nerve cells was quite a strenuous one. In order to stimulate the cells, the researchers had to inject a viral vector — a virus introduced in a particular area to alter gene expression in surrounding cells — into the arcuate nucleus. Given the incredibly miniscule size of the nucleus, this was a particularly difficult task, Zhang explained.
Ultimately, Zhang said, the hard work was worth it given the importance of the results. Zhang stated that there is a critical need to understand how the brain regulates food intake, particularly against the backdrop of growing obesity rates worldwide. Van den Pol and Zhang’s study adds to a growing body of work focused on addressing and tackling obesity and other eating disorders. A 2014 Yale study led by Tamas Horvath, director for the Yale Program on Integrative Cell Signaling and Neurobiology of Metabolism, also broke new ground in its discovery that leptin, a hormone known for its hunger-blocking effects on nerve cells inside the brain, can also affect the behavior of non-neuronal body cells. In particular, Horvath found that sets of cells that exist just outside the brain, also known as glial cells, are significantly affected by leptin.
“Glial cells provide the main barrier between the periphery and the brain,” Horvath said in a 2014 interview with Yale News. “Thus glial cells could be targeted for drugs that treat metabolic disorders, including obesity and diabetes.”
Similarly, Zhang and Van den Pol are eager to see the results of their study put to good use in the ongoing battle against metabolic disorders. Van den Pol told Yale News that he hopes the study “opens the door for further investigation” of how brain cells may contribute to obesity or other eating-related health problems.
According to data from the 2009 to 2010 National Health and Nutrition Examination Survey, more than two out of three adults in the U.S. are considered to be overweight or obese.