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DNA – Repair Protein Key to Converting Carbs to Fat?



Dr. Hei Sook Sul

Dr. Hei Sook Sul

Yesterday, I had the pleasure of listening to Hei Sook Sul (picture) from the University of California, Berkeley, who spoke at the Alberta Diabetes Institute here in Edmonton (host Dennis Vance).

Sul’s group, which works on better understanding the molecular mechanisms underlying the synthesis of fatty acids, recently identified DNA-PK, a protein kinase that plays a role in DNA repair, as a possible key factor in the activation of fatty acid synthase (FAS), the enzyme that helps convert dietary carbohydrates to fat.

In a paper, recently published in the journal Cell, Sul’s group showed that feeding high-carb diets to mice with a disabled DNA-PK gene resulted in lower levels of body fat than in their normal counterparts. This was evidently due to their inability to convert carbs to fats, a key step when excess calories from carbs need to be stored for future use.

As always, one must be careful in jumping from findings in mice to humans, and although DNA-PK may well seem an attractive pharmacological target to prevent fat accumulation in people who eat high-carb diets, it is important not to forget that this enzyme also plays an important role in DNA repair, a possible critical factor in preventing cells from mutating into cancer cells.

Nevertheless, the elucidation of this important metabolic step – the conversion of dietary carbs to fat – is certainly a major breakthrough in our understanding of how the body metabolizes carbohydrates and definitely provides fascinating new insights into the complex workings of nutritional biology.

AMS
Edmonton, Alberta

3 Comments

  1. Very interesting, and very important work, in many areas of metabolism.

    But maybe eating no excess carbs is better than
    eating excess carbs and then taking a drug to prevent fat storage, especially if you risk bad side effects.

    It doesn’t seem sensible to develop drugs to enable people to eat a bad diet without having the predictable results of that diet.

    (It wouldn’t be medically sensible, but it would be phenomenally profitable for drug companies. And the makers of high carb / low nutrition food would be delighted – they’d make great partners. “Take this pill, eat all the carb junk food you want!” $$$)

    The only way this drug would make sense is in the case where another medical problem makes it necessary for the patient to consume excess carbs – I don’t know of such a condition, but there could well be one.

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  2. There are many people who must eat a low-protein diet due to kidney disease and a wide variety of inborn errors of metabolism. To declare that a high-carbohydrate diet is “a bad diet” is unreasonable.

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  3. Those are exactly the cases I imagined would make sense – when there is another medical problem that makes it necessary to eat a high-carb diet – as you point out, there are several, and many people could benefit from drug treatment in such cases.

    Agreed, these drugs will certainly benefit those people.

    But most people in this obesity epidemic don’t have disease or genetic problems causing obesity, they have eating problems. (personal, cultural, economic,social, etc)

    I’ll stick to my wariness that such a drug could become one of the useless or even dangerous “miracle” pills that have been sold to anybody trying to lose weight. The market and the potential profits are huge, if the drug could be sold for ordinary weight loss or weight control, not just for treating specific medical problems in a medical context.

    People see the TV ads and read the magazine ads for the latest “miracle pill” and then find a doctor to prescribe it.

    One of our cultural problems is expecting a pill to cure anything.

    This is all HYPOTHETICAL, of course. The little mice will be studied for years first.

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