Saturday, May 06, 2023

Fructose (08) Acipimox and FFAs

Just a tidy up post. I got bored with acipimox. This is why inhibiting lipolysis using acipimox doesn't make you fat.

Different acute and chronic effects of acipimox treatment on glucose and lipid metabolism in patients with type 2 diabetes

I've taken this from the top left panel of Fig 1 and removed the "day three" line so we just have the pre acipimox treatment solid line and the 28 day dashed line. I've added in red arrows to mark the acipimox dose times. Across the bottom are clock times for 24 hours:











It should come as no surprise that the AUC for FFAs on day 28 is virtually the same as that for pre treatment.

Whether this is a simple drug withdrawal effect or an effect mediated via increased size of already distended adipocytes ramping up basal lipolysis in the aftermath of being stretched by acipimox is hard to say, but the bottom line is it won't make you fat.

The beauty of linoleic acid as an obesogen is that it's there all the time from diet or released from lipid stores. All it needs is a decent level of carbohydrate induced insulin signalling for it to accentuate and you're away.

Under hypoinsulinaemia linoleic acid becomes (almost) powerless to augment insulin signalling because there's not much insulin there. Hence the efficacy of the low carbohydrate diet.

Should get back to fructose next.

Peter

2 comments:

  1. Sorry if it's been mentioned and I overlooked it, but does any of this about fructose also apply to alcohol? From what I remember from Rob Lustig's lectures, the metabolism of fructose and alcohol in the liver is almost identical.

    And here's a gratuitous off-topic but interesting link:
    https://www.nytimes.com/2023/05/04/health/long-telomeres-age-longevity.html?action=click&algo=identity&block=editors_picks_recirc&fellback=false&imp_id=235218376&impression_id=a113f190-ec24-11ed-9d5c-d91a771a82cf&index=0&pgtype=Article&pool=editors-picks-ls&region=ccolumn&req_id=790205016&surface=home-featured&variant=0_identity&action=click&module=editorContent&pgtype=Article&region=CompanionColumn&contentCollection=Trending

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  2. Hi Eric, ethanol and fructose are remarkably similar in their effects. That includes on adipocytes as well as hepatocytes.

    Anon, not sure what you mean. Both are metabolised by the same system and alcohol undoubtedly inhibits it's own conversion to acetaldehyde. I've not considered what this might do to HNE.

    Peter

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