Keto diet may not work for women

Scientists from UC 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. 

Some diets focus on eating high levels of fat and protein. Is this effective for everyone equally?

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. 

“The metabolic switch between sugar and fat — it’s amazing that we don’t understand it yet. But if we do, we can tell you if keto is right for you,” said UCR biochemist Sarah Radi. 

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…

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