Mice live longer and lose weight while eating more when FGF21 . is present

Mice live longer and lose weight while eating more when FGF21 . is present

When the liver detects low levels of the protein, it activates the cells that produce FGF21 and releases the hormone into the bloodstream. FGF21 is then carried to target cells (neurons) in the brain. These cells hit the alarm button when they see FGF21, which indicates that protein intake is too low, and the brain reacts by sending a complex set of directions that prevent the mouse from growing, alter food intake, and increase number, among other things. of calories burned. Credit: Pennington Center for Biomedical Research

A single hormone appears to orchestrate the longevity caused by a low-protein diet.

A new study from the Pennington Center for Biomedical Research, published in the journal Nature CommunicationsIt was found that reducing the amount of protein in the diet produced a range of positive health outcomes, including extended life, and that these effects depended on a liver-derived metabolic hormone called Fibroblast Growth Factor 21 (FGF21).

It has long been known that reducing the amount you eat improves health and extends life, and there has been increasing interest in the possibility that reducing your protein or amino acid intake could contribute to this beneficial effect. Several recent studies suggest that diets that are low in protein, but not so low as to lead to malnutrition, can improve health. Conversely, excessive consumption of high-protein diets has been linked to increased mortality in some age groups.

A few years ago, the Neuro-Signal Lab at Pennington Biomedical discovered that the metabolic hormone FGF21 was a key signal connecting the body to the brain during protein restriction. Without this signal, the young mice failed to change their nutritional or metabolic behavior when placed on a low-protein diet.

“Our data indicate that FGF21 speaks to the brain, and that without this signal, the mouse does not know it is eating a low-protein diet. As a result, the mouse fails to adaptively alter its metabolism or dietary behavior,” said Christopher Morrison, PhD, professor and director of the Neurological Signaling Laboratory. .

The group’s latest work, led by postdoctoral researcher Cristal M. Hill, shows that low-protein diets produce beneficial metabolic effects in aging mice, improving metabolic health, reducing weakness, and extending life. These beneficial effects were also seen when protein intake was reduced in middle-aged mice, even protecting against the damages of obesity. Importantly, these beneficial effects were lost in mice lacking FGF21, indicating that its effect in the brain is critical for increasing health and lifespan.

“We have previously shown that FGF21 acts in the brain to improve metabolic health in young mice fed a low-protein diet. This new data extends this work by demonstrating that FGF21 also improves metabolic health and extends life. Altogether, these data provide Clear evidence that FGF21 is the first known hormone to orchestrate nutritional behavior and metabolic health to improve lifespan during protein restriction,” said Dr. Hill.

However, Dr. Hill said many questions remain. It is unclear exactly how these observations will translate to human aging, but the hope is that this work will reveal new molecular and neural pathways that can be leveraged to improve human health.

“This ground-breaking research has important implications for extending people’s health and life. If scientists can better understand how diets and food hormones such as FGF21 work to extend life, these discoveries could offset many health problems that occur in middle age and beyond,” said Director Pennington Biomedical Executive John Kirwan, Ph.D.

Researchers discover a new pathway to improve metabolic health

more information:
Cristal M. Hill et al, FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice, Nature Communications (2022). DOI: 10.1038 / s41467-022-29499-8

Presented by the Pennington Center for Biomedical Research

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2022-05-13 14:14:14

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