Progesterone inhibits PDH and increases insulin resistance?
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Just googling certain things like “progesterone effect on PDH, or progesterone effect on insulin” gives me conflicting research from what I’ve learned from Peat.
How do we make sense of this within the bio energetic framework?
https://pubmed.ncbi.nlm.nih.gov/28928113/
“Rather, we find that the pregnancy hormone progesterone induces PDK4 (pyruvate dehydrogenase kinase 4) in cardiomyocytes and that elevated PDK4 levels in late pregnancy lead to inhibition of PDH (pyruvate dehydrogenase) and pyruvate flux into the tricarboxylic acid cycle. Blocking PDK4 reverses the metabolic changes seen in hearts in late pregnancy.”
“To clarify the involvement of progesterone in the pathophysiology of insulin resistance during pregnancy, we examined the molecular mechanism by which progesterone affects insulin's metabolic signaling, leading to glucose uptake in 3T3-L1 adipocytes. Here, we show that progesterone causes insulin resistance by multiple mechanisms. Progesterone suppressed the PI 3-kinase pathway by promoting IRS-1 degradation and suppressed the subsequent phosphorylation of Akt. In addition, progesterone inhibited GLUT4 translocation and glucose uptake in a step distal to Akt phosphorylation. Furthermore, progesterone inhibited TC10 activation by suppressing insulin-induced Cbl phosphorylation.”
Any ideas y’all?
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No. 1: the progesterone for this experiment was dissolved in sesame oil whis is very bad.
https://pmc.ncbi.nlm.nih.gov/articles/instance/5722682/bin/NIHMS908838-supplement-311456_Online.pdfNo. 2: no word about the type of progesterone used. Could be a synthetic version which often act as estrogen not progesterone, Peat has written extensively about this.
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Wouldn't it be a tiny amount of oil though? That shouldn't really be the issue.
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Although I would be against using PUFA's, the small amounts, especially with a whole oil with its Vitamin E intact is probably nothing. This actually seems to be yet another nefarious use of the word "progesterone" when referring to progestins. In fact the premise of the experiment is based on progestin.
"...enlarged adipocytes and decreased insulin sensitivity were observed in surgical postmenopausal monkeys treated with estrogen and medroxyprogesterone acetate (34).
That is NOT progesterone, that is a progestin.
There are NUMEROUS bullshit studies like these, with word play. Do not be fooled. Same goes for many, many sugar studies use the clandestine use of PUFA, without putting any focus on it. Simply blaming the negative outcomes on sugar itself.
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@bio3nergetic I appreciate that.
The study showing the inhibition of PDH seems to use P4. Is that not real progesterone?
“ By what mechanism is PDK4 gene expression induced in late pregnancy? To investigate this question, isolated neonatal rat ventricular myocytes (NRVMs) were treated with various pregnancy hormones. While neither estrogen nor prolactin altered expression, progesterone increased PDK4 expression more than 8-fold (Figure 4D). Progesterone is induced during pregnancy, both in mice and humans12. To test if the progesterone receptor is required for this effect, we used a receptor partial agonist/antagonist, mifepristone (RU486) to pre-treat NRVMs for one hour prior to progesterone incubation. Mifepristone treatment alone led to a modest increase in PDK4 expression due to its partial agonist activity. The induction of PDK4 by progesterone, however, was fully blocked in the presence of mifepristone, indicating that the induction is progesterone receptor-mediated (Figure 4E). “
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@haidut ?
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@BroJonas Yes, indeed. P4 refers to medroxyprogesterone acetate, which is in fact a progestin. NOT progesterone. The clowns then use other big pharma poisons to passively show they are still the hero, like mifepristone to oppose the progestins actions and say "look progesterone is a real devil."
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@bio3nergetic Dude thank you so much. Without Peat and this community there would be darkness. Literally how would we figure this out on our own
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@BroJonas Any time my friend.
My world and perspective was changed, starting around 2014 finding Peat and changing my thinking. Along with that my long-time ailment, gone.
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@bio3nergetic it's a double whammy
estrogenic substance dissolved in a estrongenic substance -
@natureman lol fun for all
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@BroJonas they do study medroxyprogesterone as if its progesterone sometimes when it isnt but for that 1st study thats progesterone (also elevates in pregnancy in supplementary materials)
which seems confusing at first but:
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might only be relevant in high doses found in pregnancy (1mg per mouse is like 200mg-300mg highly absorbed, so 1g+ orally) ,
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its organ specific ( basically what the study's showing is in high doses progesterone probably switches glucose oxidation in some places so there's enough glucose for the fetus to use to grow well. i bet it really kicks in when the brain is developing more near the end)
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@cs3000 I think the glucose aspect is a balanced view of it, IF we are truly considering real progesterone, in a real woman who is pregnant. The key point here is it is not a total metabolic derangement, as even the study points out it is not at the insulin signaling level.
The second thing to keep in mind is, fatty acid composition of the organism is not being considered. In the sciences, most of these experiments don't consider these factors.
If the organism is not corrupted with PUFA throughout its tissues, Life does its thing. And it does it through a mechanism to allow the most abundance of glucose for the fetus. Are we to think that pregnancy ends Life? That doesn't make much sense. So I think the problem of dismissal of fatty acid composition, coupled with the use of PROGESTIN in the actual experiments can allow them to reach an end point they are starting with in the first place. They are reaching, and it is to imply a specific villainized idea about progesterone. That is the reason the verbiage and nomenclature is always mixed up and tricky. IF they want to make something clear, why wouldn't the language be clear!
Once again, for those who doubt it, even in that first study, if you go diving and find the reference for the supplemental material, it shows you they ONLY used progestins as well as confounders of ESTROGEN! The idea of true progesterone is merely suggestive as they allude to it. They are otherwise still using progestin. It reads:
"Mice were exposed to Estradiol (E2, 5 mg) and progesterone (P4, 1 mg), versus vehicle (n=3) or untreated (n=3) control, daily for 14 days (controls were pooled). The hormones were dissolved in sesame oil, and delivered subcutaneously.
Let's say we are assuming their implications of suggesting progesterone is bad for the heart, what then would have been an actually better approach? To monitor a population of women, collect information on the average diets, show your metabolic focal point, BUT then demonstrate actual health issues that arise from that. This way we know or at least acknowledge we are trying to know the causes (diet, exposures, etc) as well as if there is a real health issue that results from it. Otherwise you are merely pointing to a physiological, Life is Life process, and implying the rest.