Here’s What Works Better
By UNIVERSITY OF CALIFORNIA -
RIVERSIDE
UC Riverside scientists are trying to find the molecular basis of popular diets such as keto and intermittent fasting.
Scientists from University of California, Riverside are studying
how the popular keto and intermittent fasting diets work on a molecular level,
and whether both sexes benefit from them equally.
The idea behind the keto diet is that low levels of carbohydrates
and very high levels of fat and protein will force the body to use fat as fuel,
resulting in weight loss. Legions of people swear by it, and innumerable
companies produce foods designed for those people.
Intermittent fasting operates on a similar principle, restricting
eating to a small window of time during the day. During the hours without food,
the body exhausts its stores of sugar and switches to burning fat. The fat gets
converted to ketone bodies that the brain can use as fuel.
Despite their popularity, scientists have not yet identified the
genes or proteins that enable the diets to work — if they work at all.
With the keto diet, you restrict carbohydrates while eating fat and protein, such as meat.
A new, $2 million grant from the National Institutes of Health
will allow Radi and cell biology professor Frances Sladek to investigate that
switch. They believe they already have a sense of how it might work.
The key is likely a protein called HNF4 found at high levels in
the liver. It is a transcription factor, which converts DNA into RNA, which is then made
into new proteins, and it comes in two forms, P1 or P2.
The UCR-led team originally investigated P2 as a pro-cancer
protein. They didn’t find a link to cancer, but they did notice mice with high
levels of P2 in their livers also had different genes for metabolism.
They also learned that P2 shows up in greater quantity later in
the day, which could explain why mice didn’t gain nearly as much weight if the
time they eat was restricted — even if the mice ate too much.
Radi suspects an energy-sensing enzyme could cause the switch
between P1 and P2, which could then enable the process of burning fat for
energy. “That’s what we’re trying to prove,” she said.
Special attention will be paid in this study to the ways male and
female mice respond to the keto and intermittent fasting diets. Some research
suggests there are differences.
“Keto doesn’t appear to work as well for women, because we
metabolize fat differently and have different genes turned on and off in
response to fasting,” Sladek said. “But we really do not know why that is nor
how it happens — that is what we are hoping to learn.”
Whether the diet is effective for any sex, the researchers caution
against taking any diet to an extreme. It’s not clear whether all of the fat
gets metabolized on a keto or fasting diet, or whether a lot of it just
accumulates in the body. Standard Japanese diets contain 20% fat, American
diets average 35%, and keto diets can contain up to 70 or 80%, which is likely
an unsustainably high amount.
“If you eat a lot of fat, it will eventually make you fat. If you
eat too much of anything it will make you fat — including carrots,” Sladek
said. “Ultimately, the most important thing is the amount you eat, what you
eat, and the time of day that you eat.”
