Random, interesting studies
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"In vitro, 5-HT inhibits rat prostate branching through down-regulation of androgen receptor (AR). "
"...Tph1 knockout mice present higher prostate mass and up-regulation of AR when compared to wild-type,..."
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@Mauritio said in Random, interesting studies:
It seems to come down to age as well.
Here it gets interesting: if you're under 65 and eating a high protein diet, that is strongly associated with death, cancer and diabetes . Over 65 it seems to be protective !"...aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer and diabetes mortality..."
https://pmc.ncbi.nlm.nih.gov/articles/PMC3988Another pointer in this direction.
Young mice experienced a 17% decrease in life span when methionine was increased, for old mice it didn't change anything.
So maybe there is an age related effect of protein on the body.
If that's true (and that's still a big if), then im starting to wonder how good Rays low protein phase was shortly before his death, given his advanced age."The lifespan of old mice was unchanged by feeding 0.05M methionine. Young mice, however, experienced a 16.9% decrease in their average lifespan and a decreased maximum lifespan when given supplemental methionine. "
https://www.sciencedirect.com/science/article/abs/pii/0531556584900494I have previously speculated that the mechanism might have to do with the immune system, since a low protein diet can lower thymus weight and that is possibly worse than additional protein in old age .
It could also have to do with heavy metals since amino acids have heavy metal cheating properties and heavy metals tend to accumulate in old age.
https://www.sciencedirect.com/science/article/abs/pii/S2210271X25000076#:~:text=Introduction,4]%2C [5]. -
Thyroid Hormone-Induced Expression of the Hepatic Scaffold Proteins Sestrin2, β-Klotho, and FRS2α in Relation to FGF21-AMPK Signaling
https://pubmed.ncbi.nlm.nih.gov/28895643/ -
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@lobotomize-me said in Random, interesting studies:
Sodium butyrate increases seratonin
: Peripheral (gut) serotonin: In vitro and in vivo studies show that butyrate stimulates tryptophan hydroxylase‑1 (TPH1), the rate‑limiting enzyme for serotonin synthesis in intestinal enterochromaffin cells. Low concentrations of sodium butyrate (0.5–1 mM) increased TPH1 mRNA expression in human EC cells by 2.5–3.5‑fold; high concentrations (>2 mM) suppressed TPH1. A review notes that butyrate in the gut lumen can activate a zinc‑finger transcription factor (ZBP‑89) and stimulate serotonin production in enterochromaffin cells.
Central (brain) serotonin: In mice exposed to chronic unpredictable stress, sodium butyrate treatment alleviated depression‑like behaviours and increased brain serotonin (5‑HT) concentration and brain‑derived neurotrophic factor (BDNF) levels. A gene‑expression study in rats showed that sodium‑butyrate‑induced HDAC inhibition downregulated the 5‑HT₂A receptor in the brain and another study reported up‑regulation of 5‑HT₁A receptor mRNA when sodium butyrate was combined with estrogen therapy (data from behavioural tests) – suggesting receptor‑level modulation rather than direct synthesis of serotonin
SB prevented behavioural deficit made by CUMS
by raising seratonin and BDNF
https://pubmed.ncbi.nlm.nih.gov/26957230/Increase seratonin under stress:
https://pubmed.ncbi.nlm.nih.gov/18817816/https://pmc.ncbi.nlm.nih.gov/articles/PMC4396604/
"When mice were treated with antibiotics to deplete gut microbiota, serotonin levels dropped significantly.
Recolonization of the microbiota or administration of SCFAs restored normal 5-HT levels in the colon"
This means sodium butyrate could be the pathway, gut bacteria use to trigger serotonin production
️https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1035538/full
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HPβCD = 2-Hydroxypropyl-beta-Cyclodextrin = OHp-betadex has some interesting properties.
As the other cyclodextrins it provides hydrophilicity outside but the ability for hydrophobic compounds to lodge in its inner core. While the OH-p extension AFAIK widely prevents its deconstruction to glucose by amylases and makes for higher solubility in water compared to simple cyclodextrins.
The cyclodextrins seem to provide an especially outstanding fit for binding lipids (fatty acids).
Plus they have been shown to stimulate autophagic flux. Maybe both mechanisms work hand-in-hand.Here's a self-experimenter's case report of 18 i.v. treatments over 36 days as a 20% in 0.9% NaCl solution:
2-Hydroxypropyl-Β-Cyclodextrin Reduces Atherosclerotic Plaques in Human Coronary Artery
It also appeared to improve renal functions wrt albumin retention.There's a MD James C. Roberts who has collected a few more bits on such atherosclerosis reversion on his website: https://www.heartfixer.com/IndexCHC.htm
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@CrumblingCookie Thanks; this is useful information. Heartfixer.com had dropped off my radar screen.
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A pulsed magnetic field was more effective for biliary sludge (gallstone precursor) then medicamentous therapy.
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@Mauritio for some reason it makes my foot hurt in a plantar facitis manner
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@lobotomize-me what ?
Dare to think.
My X:
x.com/Metabolicmonstr -
@Mauritio eating pomegranates makes my foot ache
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Pharmacological correction of obesity-induced autophagy arrest using calcium channel blockers
https://pmc.ncbi.nlm.nih.gov/articles/PMC4157315/
4 month-old C57BL/6 male mice kept on HFD for two months were subjected to daily administration of PBS (Con, n = 4) or verapamil (Ver, 25 mg kg−1 body weight, i.p., n = 3) for 10 days. LFD-kept mice of same age (n = 5) were used as a negative control. (a, b) Liver sections were subjected to F4/80 immunostaining, which visualizes macrophage infiltration and hematoxylin counterstaining (a). F4/80-positive areas were quantified (b). (c–f) Glucose tolerance tests (GTT, c, d) and insulin tolerance tests (ITT, e, f) were conducted using indicated mice (c, e). Area-under-the-curve (AUC) was quantified from GTT and ITT data (d, f). (g) Serum insulin levels were measured from indicated mice before (Basal) and 10 min after (Glucose-stimulated) glucose injection (n = 4). (h, i) Pancreas sections were analyzed by hematoxylin and eosin (H&E) staining (h). Islet areas were quantified (i) (n = 4). Scale bar, 200 μm (a), 100 μm (h). All data are shown as mean ± s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001 (Student’s t test).
[The high fat diet effects were brought about by palmitic acid. PUFA-involvement not required.]
However, we should take into account that, even though autophagy is important for prevention of metabolic pathologies and diabetes, autophagic defects, which are correctable by calcium channel blockers, may not be the only cause for diabetes. Thus, it is feasible that calcium channel blocker-mediated restoration of the autophagic flux could not prevent the occurrence of incidental diabetes in certain cases as they may have arisen from causes other than autophagy misregulation. Nevertheless, our study does suggest that calcium channel blockers have a clinical potential for a subset of patients with NASH and type 2 diabetes whose symptoms are indeed associated with lipotoxicity-induced autophagy arrest.
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@CrumblingCookie No, the effects were not induced by palmitic acid. You misread that, as the palmitic acid is typically used as a reagent just like in this study. This is more so a case of sleight of hand with the common, "let's see how such and such thing affects metabolism or health, while we feed them high PUFA in the background." The mice had access to the common 'chow' bullshit they use in these studies. Chow is predominantly unsaturated fat. In the case of the HFD, these mice had exposure predominant amounts of C18:2 aka Linoleic acid. The so-called LFD is also mostly comprised of soybean oil.
Calcium efflux is one known mechanism of stress, which is calcium going to the wrong places; calcification. In a very specific way, when protein folding is disturbed for example, it can trigger this process. PUFA is notorious for disturbing protein synthesis as well as proper folding. This study showed, pufa exposure leading to this detrimental effect, being mitigated by calcium channel blockers. It's not news or a surprise. But better things like magnesium and or the reduction of pufa intake are better strategies,
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@bio3nergetic
I welcome your scepticism on this as I have myself seen the various and notoriously misleading studies wherein predominantly polyunsaturated FAs were foisted on the readers as a diet of saturated FAs.
With regard to autophagy however there's a distinctly inhibiting role of palmitic acid especially, it seems, according to the paragraph below and the supplementary data of the in-vitro part of this study (and others). Oleic acid or DHA did not have the same effect. They did not analyse linoleic acid's isolated effect in this and we can assume that LA is the worst but this doesn't take away the findings that PA brings about the described effects on its own. Perhaps the in-vivo results about systemic glucose and insulin will be less extreme with a different HFD richer in PA but PA's still particularly inhibitive. I agree there could be an inconsequentuality between the in-vitro reasoning and the in-vivo feeding,
yet I've looked up the chow they've used in this study for the HFD: S3282, Bio-Serv :Lard, Casein, Maltodextrin, Sucrose, Mineral Mix, Vitamin Mix, DL-Methionine, Choline Chloride
It's lard-based, which to my knowledge typically only has about 12% PUFA, and you'd probably call this ingredient list "peaty", wouldn't you? Well except for the methionine amino acid balancing.
The authors state that the mechanism here is due to inhibition of SERCA by decreasing ER membrane fluidity due to PA. Alleviating ER-stress in particular by various compounds did not negate the inhibition. It was specifically due to SERCA."During obesity and NASH, excessive fat accumulation inside hepatocytes can provoke formation of protein inclusions consisting of p62 and ubiquitinated proteins24, 28. Since the process of inclusion body formation was yet to be explored, we devised an in vitro system that made it possible to examine the effect of lipids on protein aggregation. We found that, in response to palmitic acid (PA, 500 μM), which is a long-chain saturated fatty acid (SFA) that becomes highly elevated in sera of obese individuals, human HepG2 hepatoma cells formed a considerable amount of insoluble cytoplasmic inclusions consisting of ubiquitinated proteins and p62 (Fig. 1a–c). PA-induced accumulation of protein inclusions had a proportional correlation with both dose (Supplementary Fig. 1) and time (Supplementary Fig. 2a); correspondingly, when treated for a longer period (48 hr), even a very low dose of PA (50 μM) was able to induce substantial protein inclusions (Supplementary Fig. 1b). Although prolonged treatment of high-dose PA (24 and 48 hr, 500 μM) provoked apoptosis, there was no significant cell death at 9 hr of PA treatment (Supplementary Fig. 3), a time point at which we observed the greatest amount of prominent protein inclusions (Fig. 1a–c and Supplementary Fig. 2a). The inclusions were frequently associated with condensed fibers of keratin (Supplementary Fig. 4a) or tubulin (Supplementary Fig. 4b) as observed previously for various protein aggregates28, 30. It is interesting to note that the protein aggregates were located away from the endoplasmic reticulum (ER) structure (Supplementary Fig. 4c) in which many unfolded proteins typically accumulate during lipotoxicity and obesity13. Although another SFA stearic acid (SA) was also able to induce accumulation of p62 (Supplementary Fig. 2b), unsaturated fatty acids (UFA) such as oleic acid (OA) and docosahexaenoic acid (DHA) failed to induce such accumulation (Supplementary Fig. 2c, d) and actually suppressed the effect of SFA (Supplementary Fig. 2e, f)."
"SFA, but not UFA, induced prominent accumulation of autophagosomes as manifested by increased LC3-II levels (Supplementary Fig. 2a–f). "
Do you think we should all focus more on not to neglect MUFA/oleic acid therefore rather than praising and binging on SFA?
