Image of the month: This brain region coordinates survival adaptations to food shortages

Microscopy image of a brain region that coordinates survival adaptations to food shortages. In the hippocampal dentate gyrus of the brain, SRC-2 (green) is abundantly expressed, co-localizing with several POMC-lineage neurons (red). Image courtesy of the authors/Cell Reports, 2021.

When food is not easily available or during fasting, organisms modify certain aspects of their metabolism to be able to function and of their behavior to improve the odds of restoring the much needed nutrition. In this study, work by the lab of Dr. Yong Xu at Baylor College of Medicine, and colleagues, shows new details of the neural and molecular processes involved in adapting to the lack of food. Their findings could lead to improved strategies for weight management.

SRC-2 is required for implementing metabolic adaptations to survive lack of food

Xu, professor of pediatricsnutrition and molecular and cellular biology at Baylor, and his colleagues looked into two important metabolic components: energy expenditure and blood glucose balance.

“One way to adapt to lack of food is to reduce how much energy the body spends. It is also important that the body maintains a glucose balance that sustains brain activity,” Xu said.

Dr. Yong Xu

The team found that a molecule known as steroid receptor coactivator-2 (SRC-2) specifically in POMC neurons in the hypothalamus, a brain region involved in various aspects of metabolism, including energy management, is required to retain the ability to reduce energy expenditure and to maintain glucose levels that allow the animal to survive until food is available again.

SRC-2 also is required to carry out behavioral adaptations to overcome lack of food

The researchers also looked into behavioral adaptations that help the animal find food.

“When an animal living in the wild has not eaten in a while, it needs to venture into its environment to search for food, which at the same time exposes it to predators, creating anxiety,” Xu said. “We found that SRC-2 helps overcome the anxiety triggered by the need to go out to feed, facilitating the search for food.”

In addition, the researchers found that SRC-2 is required to delay the normal satiety signal that stops the animal from eating. “Delaying the satiety signal stimulates the animal to engage in continuous feeding behavior longer, eating as much as possible, quickly, to reduce the time they are exposed to a dangerous environment.”

During most of evolution, having enough food has been, and still is, the first priority of animals in the wild.

Xu and colleagues propose that SRC-2 is evolutionarily conserved, meaning that it is at the center of the regulation of animal metabolic and behavioral adaptations that help organisms survive when food is not easily available.

On the other hand, when the environment changes so that food is readily available, animals can eat without limitations. “In this case, SRC-2 becomes detrimental to the animals. It facilitates overeating, leading to weight gain and obesity,” Xu said.

At the mechanistic level, Xu and colleagues found that SRC-2 controls the ability of POMC neurons to transmit electric signals to communicate with other neurons. SRC-2 also mediates its effects by regulating the expression of multiple genes.

Are you interested in all the details of this work? Find them in the journal Cell Reports.

Other contributors to this work include Yongjie Yang, Yanlin He, Hailan Liu, Wenjun Zhou, Chunmei Wang, Pingwen Xu, Xing Cai, Hesong Liu, Kaifan Yu, Zhou Pei, Ilirjana Hyseni, Makoto Fukuda, Zheng Sun, Jianming Xu and Bert W. O’Malley, all at Baylor College of Medicine. Qingchun Tong is affiliated with the University of Texas Health Science Center at Houston.

The work was supported by grants from the National Institutes of Health (R01DK114279, R01DK109934, R21NS108091, R00DK107008, R01DK104901, R01DK126655, K01DK119471, R01DK115761, R01DK117281, R01DK125480, R01DK120858, R01DK111436, R01ES027544, RF1AG069966, HL153320, AG070687, R01HD07857, R01HD008818, P01DK059820; P01DK113954 and P20 GM135002). Further support was provided by USDA/CRIS (51000-064-01S), American Diabetes Association (1-17-354 PDF-138) and American Heart Association awards (16POST27260254).

 

By Ana María Rodríguez, Ph.D.

 

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