Dr. Yong Xu, the senior author of the study, wanted to figure out what role the brain plays in weight control. The sex-weight connection proposed "a novel mechanism that may contribute to this difference between sexes."
Earlier studies have suggested two main factors – sex chromosomes and sex hormones – linked to how the body controls weight in different genders. While scientists believe that hormones have a vital role in weight maintenance, not much is known about sex chromosomes and their role in regulating body weight.
In this study, Xu and his team looked at a third group – the brain. He explained, "We think ours is among the first studies looking at the brain to understand weight control differences between males and females." This also builds up on his previous work that established the presence of neuron populations in the brain vital for weight management. (Related: Being unfit is just as bad as diabetes in terms of being at risk of cardiovascular disease.)
Differences in expression
For this paper, the researchers looked at how these neuron populations contributed to sexual dimorphism, that is, the systematic differences between individuals of different sex in the same species. In particular, they focused on pro-opiomelanocortin (POMC) neurons, nerve cells found in the hypothalamus which regulate feeding and body weight balance. They found that POMC neurons in female mice had a higher neural activity than those in the males.
"One of the most important functions of all neurons is firing electrical signals," explained Xu, a professor at the Department of Pediatrics in Baylor. "That's how neurons talk to each other and to other tissues."
The authors believed that the enhanced POMC function meant that the hypothalamus was better able to maintain the body weight of females through appetite suppression and increased energy expenditure after a high-fat diet. To understand how POMC neurons in females fired faster than their counterparts in males, the team analyzed differences in gene expression in the neuron. They found one gene, TAp63, that was expressed more in females than in males.
"We know from previous work that when we knock out the gene TAp63 in the entire body of a mouse, the animal becomes obese," Xu said. "Here, we knocked out the gene only in POMC neurons and strikingly, this change did not affect male mice. On the other hand, female mice developed male-like obesity."
Using in vivo testing, researchers bred mutated male and female mice that did not have the TAp63 gene and fed them a high-fat diet for 16 weeks. At the end of the study, researchers studied brain samples extracted from the mice and correlated these with changes in body weight and feeding habits recorded during the trials.
Researchers found that removing TAp63 in female mice greatly reduced the POMC neurons' neural activity, making it similar to that observed in males. The same result, however, was not observed in males, as knocking out TAp63 did not affect the firing rate of their neurons.
The findings presented in the study offers new ways to better understand how sexual dimorphism plays a factor in maintaining weight. In particular, that females fire higher levels of TAp63 in POMC neurons than males do could mean that they could be better protected from weight gain. The results could also pave the way for gender-specific strategies to address obesity and other metabolic disorders.
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