Remember when I said that even though fat science is a mind-boggling complicated mess, someday there could well be a magic bullet aimed at just one thing that turns out to be the simple cure for obesity – a magic bullet like penicillin or statins. Well even if you don’t remember I said it, I did say it. Investigators from Scripps Center for Metabolomics, La Jolla, California, have just reported on another candidate for that magic bullet. (1,2)
These guys have demonstrated how a center in the hypothalamus, the regulator in the brain for body temperature, works to reduce body temperature when we diet to lose weight. This is one of many ways that your body fights back when you try to lose weight. They discovered that this response is regulated by one of the several kinds of opioid receptor – the kappa opioid receptor (KOR). By blockade of KOR, but not of the delta or the mu-opioid receptor subtypes, with a drug, they fully stopped the lowering of body temperature that happens when you restrict calorie intake. This KOR blocking increased weight loss during calorie restriction independent of various degrees of calorie restriction. Also, it was seen that nothing happened when KOR was blocked in animals who were fed all they wanted to eat. Medication blockade of KOR, as well as mice genetically bred to lack this receptor, was further shown to double the weight loss during calorie restriction and make them resistant to weight gain during diet-induced obesity by overfeeding.
Before we break out the champagne we should realize that these investigations happened in mice who are different from us. For one thing, the classic diet-induced model of obesity in mice does not exist in humans. You can’t make humans fat by overfeeding them. The other thing is that God made tight body temperature control for a reason even though it uses a lot of calories. It might be dangerous. Another possible drawback to this attempt to control weight is that the main reason for the failure of diet resolutions isn’t body temperature control but the misery of constant hunger. Finally, my prediction that there will one day be a single fix might be wrong. The other prediction for the eventual cure for obesity might be more like the sixth brake solution of Harvard professor Lee M Kaplan MD expressed among other places at the Obesity Summit of 2007, in Cleveland. We’ve talked about the 6th brake solution before. Apparently your car has lots of backups for braking. It will not be until we disable up to the 6th breaking method that we start to make it impossible to stop your car – cure obesity.
1. da Silva J., Horvath TL. Metabolism: A Burning Opioid Issue in Obesity Therapeutics. https://doi.org/10.1016/j.cub.2019.10.055
2. Cintron-Colon, R., et al. (2019). Activation of kappa-opioid receptor regulates the hypothermic response to calorie restriction and limits body weight loss. Curr. Biol. 29, 4291–4299.
John DiTraglia M.D. is a Pediatrician in Portsmouth. He can be reached by e-mail- firstname.lastname@example.org or phone-354-6605.
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