Persistently high levels of a liver-produced starvation hormone, known as FGF21, significantly stop the growth of mice, scientists at the University of Texas Southwestern Medical Center have discovered.
Writing about their findings in the journal Cell Metabolism, the researchers said that the hormone does so by causing the mice to become resistant to growth hormone.
Advertisement"It was an unexpected finding. In starvation, (it was known that) growth hormone goes down. This might explain much of the mechanism responsible," said David Mangelsdorf of the medical school.
In a previous study, the researchers had shown that FGF21 shifts the metabolism of mice to a fat-burning mode and induces a state of energy-conserving torpor.
Studies have also shown that this hormone acts as an insulin sensitizer.
In their latest work, Mangelsdorf and study coauthor Steven Kliewer have uncovered the physiological role that this hormone plays in promoting energy conservation when animals go without food.
The researchers have discovered that mice with higher-than-normal levels of FGF21 are normally sized at birth, but they gain less weight and their bones grow less.
Upon further experimentation, the researchers observed that FGF21 reduced concentrations of a growth hormone-mediating transcription factor (a gene that controls the activity of other genes), leading to a decline in the expression of its target genes, including insulin-like growth factor 1 (IGF-1).
Mangelsdorf says that the earlier discovery of FGF21's effects on fat metabolism and insulin response have led to considerable interest in its potential use as a type 2 diabetes drug, and thus it becomes important to understand what else the hormone may do.
As regards positive effects of FGF21, the researchers say that its growth hormone actions as well as insulin effects support the notion that it might extend lifespan, a hypothesis they want to explore.
The researchers say that chronically blocking growth hormone could have many other ill effects.
Mangelsdorf believes that the new findings may be helpful in understanding the action of fibrate drugs, which are used these days to treat patients with metabolic syndrome, because such medication target a receptor known as PPARa, which is necessary for rise in FGF21 that occurs in fasted mice.
"This finding together with data showing that FGF21 expression is induced by PPARa agonists in primary human (liver cells) suggest that the PPARa/FGF21 pathway may be operative and affect IGF-1 signalling in humans," say the researchers.