ESPEYB15 15 Editor’s Choice Obesity must be studied separately in men and women (1 abstracts)
15.12 TAp63 contributes to sexual dimorphism in POMC neuron functions and energy homeostasis
Wang C , He Y , Xu P , Yang Y , Saito K , Xia Y , Yan X , Hinton Jr A , Yan C & Ding H
To read the full abstract: Nature Communications 2018;9:1544
Obesity prevalence is generally higher in women than in men, and there is also a sex difference in body fat distribution. Sex differences in obesity can be explained in part by the influence of gonadal steroids on body composition and appetite; however, behavioural, and socio-cultural factors may also play a role. Here is the advantage of experimental animals: when male and female mice eat the same high-fat diet, males gain more weight than females. Is it the sex chromosomes or the sex hormones that leads to this sexual dimorphism?
Here, the authors compared the firing rate of many types of neurons of males and females and found a few that fired differently, including POMC neurons; female POMC neurons (anti orexigenic) fire faster than male neurons. They show that TAp63 gene, knockout of which causes obesity, is expressed more in females than in males. Selective knockout of the gene only in POMC neurons did not affect male mice, but, female mice developed male-like obesity and decreased the firing activity to the level of males. The story then goes as follows: female POMC neurons express more TAp63, which makes their POMC neurons to fire faster than males. This results in the females having less appetite, spending more energy and therefore being protected from gaining weight, which is nice in our current energy-rich life-style, but gave males an advantage in a thrifty environment. Obviously, females must also have other mechanisms to maintain their adipose tissue, and the bottom-line is that females tend to have more adiposity than males in our modern life-style. It means also that both animal and clinical research on obesity must be designed and analyzed to separately examine both men and women.
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ESPE Yearbook of Paediatric Endocrinology
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