Brain blamed for male mice gaining more weight than females

April 18 (UPI) — Researchers have determined why they believe male mice traditionally gain more weight than females — and the answer likely involves neurons in the brain, according to a new study.

While the study was with mice, researchers say that a genetic finding in a region of the brain responsible for the speed at which specific neurons fire — and which has an effect on appetite and energy expenditure — could lead to personalized treatment for obesity and other metabolic conditions.

Previous research has shown that while male and female mice may eat the same high-fat diet, but males gain significantly more weight than the females. Scientists at the Baylor College of Medicine in Houston studied the phenomenon in mice, publishing their findings Wednesday in the journal Nature Communications.

“Differences in sex chromosomes and in sex hormones are important, but we have always wondered whether there is a third group of factors that may also contribute to the sex differences in the ability to regulate body weight,” Dr. Yong Xu, of the Children’s Nutrition Research Center at Baylor College of Medicine and Texas Children’s Hospital, said in a press release. “We think ours is among the first studies looking at the brain to understand weight control differences between males and females.”

With males having one X and one Y chromosome, and females two X chromosomes, scientists don’t know which genes on the sex chromosomes contribute to this issue.

Researchers think that hormones also may regulate body weight. Testosterone is the major sex hormone in males, and female generally have high levels of estrogen and progesterone in their blood.

Aware that previous studies had shown that neurons in the brain are very important for weight control, the researchers wanted to know whether it was different in male and female mice.

“One of the most important functions of all neurons is firing electrical signals. That’s how neurons talk to each other and to other tissues,” Xu said. “We compared the firing rate of many types of neurons between males and females and found a few that fired differently.”

The researchers focused one type, POMC neurons in the hypothalamus, which the researchers say helps maintain normal body weight by inhibiting appetite and promoting energy expenditure in response to a chronic high fat diet.

By testing the firing rate of POMC neurons using electrophysiological techniques, the researchers found female POMC neurons are faster than male neurons.

To find why female POMC neurons fire faster, the researchers screened them for gene expression, finding that one gene, TAp63, is 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.”

By knocking out TAp63, it also decreased the firing activity of female POMC neurons to be more similar to those in a male. Conversely, knocking out TAp63 in males did not affect the firing rate of their POMC neurons.

The researchers believe the finding could lead to the development of gender-specific therapeutic strategies for obesity and metabolic disorders.

“We think that our findings suggest that, in addition to studying chromosome and hormonal differences between males and females, scientists should also pay attention to this third category of factors,” Xu said.

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