Scimex: A small molecule that binds to a receptor found on muscle cells speeds
up energy metabolism—but only in female mice. In an article published
online on March 5 in Chemistry & Biology, researchers show that
female mice treated with a molecule found in tree leaves could indulge
in high-fat foods without gaining weight or accumulating fat. Males did
not enjoy similar benefits, highlighting the need to study both sexes
while developing drugs for obesity and other conditions.
"An equivalent diet pill in humans would allow women to eat or drink
whatever they wanted," says senior author Dr. Keqiang Ye, of the Emory
University School of Medicine in Atlanta. "The pill would burn calories
without affecting appetite."
Research has shown that a hormone called brain-derived neurotrophic
factor (BDNF), which is secreted after physical exercise, controls body
weight gain by eliciting signals to suppress food intake and enhance
energy expenditure. Manipulation of this signaling represents a
promising strategy for combating obesity; however, BDNF degrades quickly
in the body.
While developing a drug for neurological diseases, Dr. Ye and his
colleagues discovered that a small natural product called
7,8-dihydroxyflavone (7,8-DHF) that is found in Godmania aesculifolia
and primula tree leaves from Central and South America mimics the
physiological functions of BDNF. The molecule seems to work by
interfering with enzymes that acts as the body's fuel gauge.
When mice were fed 7,8-DHF along with a high-fat diet, females
maintained their appetite but kept a healthy weight and metabolic
profile without demonstrable side effects; males, on the other hand,
still developed obesity and diabetes. The mechanisms behind this sex
difference are unknown, but sex-specific hormones might play a role. For
example, estrogen has been proposed to enhance the effects of BDNF
signaling, and 7,8-DHF was reported to alter estrogen metabolism.
Dr. Ye's team has designed a biological agent that helps 7,8-DHF be
absorbed by the body. It is now heading for phase I human clinical
trials treating various BDNF-implicated neurological diseases—including
Alzheimer's—as well as obesity and diabetes.
"This drug has been extensively tested in a variety of neurological
diseases in both male and female animal models and exhibits very
promising therapeutic efficacy, suggesting that this drug is efficacious
for both sexes in the central nervous system," Ye said. "Clearly,
further investigation is necessary to explore why it selectively burns
the fat for the female mice."