Ketones inhibit lipolysis

Petro just posted a brief article about acipimox & the insulin hypothesis.  Similar to insulin’s forte, acipimox inhibits lipolysis.  This leads to expansion of adipose tissue, and eventually, weight gain.

Acipimox acts on the same receptor as niacin and ketones, GPR109a.  That is, all three of those agents inhibit lipolysis.  We’ve discussed some of the implications of this on fuel partitioning HERE.

 

ketone-supp-physiology

 

In brief, plasma lactate reflects muscle glycogen use.  During activity, you usually burn a mix of glycogen and fatty acids; more of the former with higher intensity activity (unless theoretically if you’re ketoadapted).  By inhibiting lipolysis with niacin, acipimox, or beta-hydroxybutyrate, the body is forced to rely more heavily on glycogen and this is reflected in higher plasma lactate.

 




 

Theoretically, by forcing the body into this higher intensity fuel usage, this could be a mild performance booster and might even explain the 2% advantage seen in the Cox study on ketone supps.  Probably won’t work with acipimox because it’s not a fuel; at least ketone supps are providing kcals.  Niacin: maybe, but for different reasons.

 

However, caution is warranted when taking ketone supps out of the #context of exercise.  Similar to mice given acipimox literally in the drinking water, ketone supps may promote an environment supporting expansion of adipose tissue by inhibiting lipolysis via GPR109a.

Also, ketone supps are sort-of-like empty calories; when you could be burning body fat (or glycogen), you’re displacing it with an exogenous fuel source.

 




 

So basically my advice remains unchanged: if that 2% performance advantage will benefit you, go for it.  Also potentially useful for mild cognitive impairment.  Not sure if Regular Joe’s should make ketone supps an everyday thing, though.

#context

 

 

More on ketone supps HERE.

 

I think the whole “ketones inhibit lipolysis” mechanism may have evolved *specifically* to prevent ketones from getting too high during starvation.  You’d be losing a lot of energy in the form of ketones via urinary excretion, ramping up renal gluconeogenesis, and wasting a lot of glutamine.

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