helow. i post under the user name modeaa in this forum,
http://www.acne.org/messageboard/topic/295030-repairing-the-long-term-damage-from-accutane/page-350. my english wont be the best here.
i was thinking the next: foxo gene is upregulated during accutane (
http://www.ncbi.nlnim.h.gov/pmc/articles/PMC3219165/) and i suspect that post accutane foxo is still caught up in a loop of overexpression .
ER stress- somewhere i think i read that it is causing foxo activation(or the other way around it was)
somehting called ELOVL5 which reduced by accutane can stop foxo by producing cis-vaccenic acid
http://www.jlr.org/content/54/1/71.full
Elovl5 regulates the mTORC2-Akt-FOXO1 pathway by controlling hepatic cis-vaccenic acid synthesis in diet-induced obese mice
Elevated hepatic expression of fatty acid elongase-5 (Elovl5) induces FoxO1 phosphorylation, lowers FoxO1 nuclear content, and suppresses expression of genes involved in gluconeogenesis (GNG).
http://rgd.mcw.edu/r...6067&id=1353049
''Isotretinoin results in decreased expression of ELOVL5 mRNA.''
http://www.ncbi.nlm.nih.gov/pubmed/24814977
''
Increasing hepatic Elovl5 activity in obese mice lowered hepatic TGs and endoplasmic reticulum stress markers''
http://www.genecards.org/cgi-bin/carddisp.pl?gene=ELOVL5
This gene belongs to the ELO family. It is highly expressed in the adrenal gland and testis, and e
ncodes a multi-pass membrane protein that is localized in the endoplasmic reticulum. This protein is involved in the elongation of long-chain polyunsaturated fatty acids.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851975/
''As integral components of cellular membranes, fatty acids could directly affect biologic processes relevant to the development of HF. For example, some fatty acids have been shown to enhance endoplasmic reticulum stress and inflammation, stimulate apoptosis, and impair endothelial function.''
''A precursor of cis-vaccenic acid, palmitoleic acid, may increase the risk of HF via hypertension.
27 This suggests that conversion of palmitoleic acid to cis-vaccenic acidcould mitigate blood pressure raising effect and lower the risk of HF. Additional studies are needed to elucidate biologic effects of cis-vaccenic acid in humans''
also posiible that foxo inhibition inhibit scd ezyme and this can cause a foxo loop activation.
http://diabetes.diabetesjournals.org/content/57/4/846.full
''
We show that fatty acids as well as pharmacological ER stress–inducing agents rapidly induce JNK, the ER stress response, and increase Foxo1 nuclear localization and activity at a time when Akt phosphorylation is increased.
Foxo1 activation is blocked by JNK inhibition.''
''
In various mammalian cell lines including β-cells, lower fatty acid toxicity was associated with increased cellular capacity for triglyceride synthesis and with upregulation of stearoyl CoA desaturase 1 (SCD1)''
''Possibly, fatty acid activation of Foxo1 with subsequent inhibition of SCD1 would create a self-sustained cycle with deleterious cellular effects'
also wondered if scd inhibition might cause more retinoic acid, as if post accutane the boddy produce more accutane like substences(and this will further increase/sustaine foxo?)
http://www.ncbi.nlm.nih.gov/pubmed/21573029
''We previously reported that mice with skin-specific deletion of stearoyl-CoA desaturase-1 (Scd1) recapitulated the skin phenotype and hypermetabolism observed in mice with a whole-body deletion of Scd1.''
''In this study, we first performed a diet-induced obesity experiment at thermoneutral temperature (33°C) and found that
skin-specific Scd1 knockout (SKO)mice still remain resistant to obesity.''
''We identified an extraordinary number of differentially expressed genes that support the previously documented histological observations of sebaceous gland hypoplasia, inflammation and epidermal hyperplasia in SKO mice. Additionally, transcript levels were reduced in skin of SKO mice for genes involved in fatty acid synthesis, elongation and desaturation, which may be attributed to decreased abundance of key transcription factors including SREBP1c, ChREBP and LXRα. Conversely, genes involved in cholesterol synthesis were increased, suggesting an imbalance between skin fatty acid and cholesterol synthesis. Unexpectedly,
we observed a robust elevation in skin retinol, retinoic acid and retinoic acid-induced genes in SKO mice.
Furthermore, SEB-1
sebocytes treated with retinol and SCD inhibitor also
display an elevation in retinoic acid-induced genes.
These results highlight the importance of monounsaturated fatty acid synthesis for maintaining retinol homeostasis and point to disturbed retinol metabolism as a novel contributor to the Scd1 deficiency-induced skin phenotype.''
http://www.jlr.org/content/40/9/1549.full
''The lipid composition of cellular membranes is regulated to maintain membrane fluidity. A key enzyme involved in this process is the membrane-bound stearoyl-CoA desaturase (SCD) which is the rate-limiting enzyme in the cellular synthesis of monounsaturated fatty acids from saturated fatty acids. A proper ratio of saturated to monounsaturated fatty acids contributes to membrane fluidity''
http://www.ncbi.nlm....les/PMC2835892/
''Constituents of the lipid metabolism have been shown to be important for sebaceous gland morphogenesis.
Targeted deletion of stearoyl-CoA desaturase 1 (SCD1) or mutations within the gene coding for this key enzyme of mammalian lipid metabolism (asebia mouse)
result in atrophy of sebaceous glands of the skin and Meibomian glands of the eyelid as well as abnormal hair growth''
if i remember correctly scd produce palmitoleic acid which by Elovl5 can ba enlonged to cis-vaccenic acid- which can stops foxo. this also stops er sress? how it is all connected?
more stuff maybe worth mentioning:
http://nar.oxfordjournals.org/content/early/2014/08/20/nar.gku766.full.pdf
''The expression of Elovl5, which exhibits a weak oscillation, and peak expression of the clock output gene,
Nocturnin (
Ccrn4l) at ZT12
were also repressed in RORγ−/− liver, ''
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431109/
''Hepatic Elovl-5 expression, however, is induced during postnatal development, in leptin deficiency, and by pharmacological ligands for PPARα (
17).''
i was thinking that taking sea buckthorn oil which contain palmitoleic acid and cis-vaccenic acid can stop this hypotized foxo/er stress loop post accutane. and also that it should be in low dose for not athropy the body enzyme own production of those fatty acids. what do you think bout all this(theory)?
thanks for reading
edit:why it's posted it like that?
(Moderator -- have fixed it for you)
I have some (can't remember what I was taking it for now, LOL) but stopped because there seemed to be some information that suggested it could cause insomnia, which I don't need. But now I'm going to dig out my bottle and give it a whirl.
