Inhibiting lipolysis using acipimox

Okay, time to start doing a little blogging again. I've been thinking about various aspects of free fatty acids largely derived from studies using acipimox, like this one:

Inhibition of Lipolysis Ameliorates Diabetic Phenotype in a Mouse Model of Obstructive Sleep Apnea

I consider that one primary action of insulin is to inhibit lipolysis. Which makes it a driver of weight gain. Or, rather, it makes it a mediator of calorie trapping within adipocytes, which drives hunger (you needed those trapped calories), said hunger then gets the blame for the swollen adipocytes. You know, humans only get fat by eating too much. Ask any obesity researcher.

So what is the effect of other inhibitors of lipolysis on adipocyte size? The classic, freely available inhibitor of lipolysis is acipimox. Does acipimox make you fat? There is nothing on the patient information leaflet or data sheet about weight gain. Being hungry while you take it is only mentioned as a side effect in anecdotal reports from the poor folks taking the stuff. Of course the link between being hungry and gaining weight is easily eliminated by a simple matter of willpower. Again, ask any obesity researcher.

The published clinical research with acipimox (which is interesting) is usually of too short a duration to show weight changes, most studies usually last a few days or a couple of weeks.

So eventually I found an animal model using acipimox. It was looking at intermittent hypoxia (termed IH below) and weight loss (also very interesting, another day) but it came up with this little gem:

"Acipimox treatment [prevented IH-induced lipolysis and] increased epididymal fat mass and adipocyte size by 19% and 10%, respectively".

Acipimox, given to mice eating standard mouse crapinabag, causes weight gain, more especially fat gain. It does not cause hypoglycaemia and any appetite stimulation is likely to be because adipocytes have accepted dietary fat and are not letting it go.

Just as insulin denies lipolysis and so distends adipocytes, so too does acipimox. Acipimox, unlike insulin, does not drive potentially fatal hypoglycaemia with subsequent life saving food ingestion to explain away the weight gain.

This is where I started with acipimox: does it cause weight gain? Yes, inhibiting lipolysis, without using insulin, causes weight gain.

Of course, no one uses acipimox to cause weight gain. It is usually used to decrease plasma free fatty acids with a view to improving some aspect of metabolic function.

Which of course leads on to the monogenetic insulin resistance paper cited by Ivor on Facebook...

Peter