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I had read that some diabetes meds help stimulate seb glands and invigorate skin moisture and oil systems via the PPARs. I assumed these were all internal medications, but I just found out that there are actually topical PPAR stimulators (GW1514 for example).

my damage from accutane is basically isolated to my face, so obviously a topical treatment is appealing since i can just apply it to the affeat areas.


However, I feel like I've mentioned PPAR stimulators to my dermatologist before, yet he sort of shook his head. He has an MD and a PHD, so I can't really question him, but at the time i was under the impression that PPAR stims were internal....but topical seems less severe/risky?

Does anyone know why PPAR stims havent been uses for skin conditions much? what are the downfalls?

I took accutane 5 years ago and have permanent damage: Now my face has skin fragility and thinness, extreme dryness and wrinkling, inflammation and irritation, dyshesion and diminished waterproofing, as the skin barrier homeostasis has been disrupted, etc. etc.

about 1 year ago i started taking adderall for adhd. and this has made my skin condition worse. i dont want to downplay how adderall has worsened my skin....but I have a classmate that I see who takes about 10 times my dose and is about 60 pounds lighter than me yet doesnt have skin issues remotely as bad as mine.


Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes.
Schmuth M, Haqq CM, Cairns WJ, Holder JC, Dorsam S, Chang S, Lau P, Fowler AJ, Chuang G, Moser AH, Brown BE, Mao-Qiang M, Uchida Y, Schoonjans K, Auwerx J, Chambon P, Willson TM, Elias PM, Feingold KR.

Department of Medicine, University of California, San Francisco, California, USA.
Erratum in:

J Invest Dermatol. 2004 Oct;123(4):806.
Peroxisome proliferator-activated receptor (PPAR) are nuclear hormone receptors that are activated by endogenous lipid metabolites. Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier homeostasis. Recent studies have shown that PPAR-beta/delta activation induces keratinocyte differentiation in vitro. This study demonstrated that topical treatment of mice with a selective PPAR-beta/delta agonist (GW1514) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation [corrected]. In contrast to PPAR-alpha activation, PPAR-beta/deltain vivo did not display anti-proliferative or pro-apoptotic effects. The pro-differentiating effects persisted in mice lacking PPAR-alpha, but were decreased in mice deficient in retinoid X receptor-alpha, the major heterodimerization partner of PPAR. Furthermore, in vitro PPAR-beta/delta activation, aside from stimulating differentiation-related genes, additionally induced adipose differentiation-related protein (ADRP) and fasting induced adipose factor (FIAF) mRNA in cultures keratinocytes, which was paralleled by increased oil red O staining indicative of lipid accumulation, the bulk of which were triglycerides (TG). Comparison of differentially expressed genes between PPAR-beta/delta and PPAR-alpha activation revealed distinct profiles. Together, these studies indicate that PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates TG accumulation in keratinocytes.
 

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did I miss something here??? this makes no sense to me what so ever-
 

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my understanding is not very sophisticated either. but basically PPAR means peroxisome proliferator activated receptors, and stimulating these receptors are thought to stimulated sebaceous production of lipids. these are important for giving ur skin a slick barrier, waterproofing, keeping moisture in the skin (instead of letting it evaporate). although sebum/sebaceous glands are also responsible for acne. in my case, accutane has completely shut down these sebaceous glands so my face is literally dry like wood and can get rough like sandpaper. lac hydrin helped the roughness, but my skin is also thinned out, so lac hydrin makes it feel very delicated and tight, though smooth.


....furthermore, some of the other lipids that PPAR stimulation seems to produce also thicken some layers of the skin, and thinning of the skin results in wrinkles. Accutane is known to thin the skin. hence why im wondering if PPAR stimulators can combat this permanent side effect.

Below is another article. They all some promising about the role of PPAR stimulators in skin disorders involving the skin barrier, yet i dont think ive heard of people using them.


Basis for Improved Permeability Barrier Homeostasis
Induced by PPAR and LXR Activators: Liposensors
Stimulate Lipid Synthesis, Lamellar Body Secretion,
and Post-Secretory Lipid Processing
Mao-Qiang Man1, Eung-Ho Choi1, Matt Schmuth1, Debra Crumrine1, Yoshikazu Uchida1, Peter M. Elias1,
Walter M. Holleran1 and Kenneth R. Feingold1,2
Previously, we demonstrated that topical applications of peroxisome proliferator-activated receptors (PPARs)
and liver X receptor (LXR) activators improve permeability barrier homeostasis. We showed further that
stimulation of epidermal differentiation provides one mechanism that could account for such improvement.
Here, we studied the effects of these agents on the lipid matrix of the stratum corneum. Hairless mice were
treated topically with activators of PPARa (WY14643), PPARd (GW1514), PPARg (ciglitazone), and LXR (22(R)-
cholesterol or TO901317) or vehicle twice daily for 3 days. All activators significantly increased epidermal
cholesterol, fatty acid, and sphingolipid synthesis, including the production of barrier-specific ceramide
species. In addition, lamellar body (LB) formation, secretion, and post-secretory processing accelerated
significantly following acute barrier disruption in PPAR/LXR-activator-treated animals. Finally, the activity of
epidermal b-glucocerebrosidase, a key lipid-processing enzyme, increased in PPAR/LXR-activator-treated
animals. Thus, topical PPAR and LXR activators stimulate epidermal lipid synthesis, increase LB secretion, and
accelerate extracellular lipid processing, providing additional mechanisms that further account for their ability
to improve epidermal permeability barrier homeostasis. Since the liposensors are activated by endogenous
lipid metabolites, they may serve as unique regulators of barrier homeostasis.
 

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I took Accutane myself and can't say that it thinned my skin.
 

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I had read that some diabetes meds help stimulate seb glands and invigorate skin moisture and oil systems via the PPARs. I assumed these were all internal medications, but I just found out that there are actually topical PPAR stimulators (GW1514 for example).

my damage from accutane is basically isolated to my face, so obviously a topical treatment is appealing since i can just apply it to the affeat areas.


However, I feel like I've mentioned PPAR stimulators to my dermatologist before, yet he sort of shook his head. He has an MD and a PHD, so I can't really question him, but at the time i was under the impression that PPAR stims were internal....but topical seems less severe/risky?

Does anyone know why PPAR stims havent been uses for skin conditions much? what are the downfalls?

I took accutane 5 years ago and have permanent damage: Now my face has skin fragility and thinness, extreme dryness and wrinkling, inflammation and irritation, dyshesion and diminished waterproofing, as the skin barrier homeostasis has been disrupted, etc. etc.

about 1 year ago i started taking adderall for adhd. and this has made my skin condition worse. i dont want to downplay how adderall has worsened my skin....but I have a classmate that I see who takes about 10 times my dose and is about 60 pounds lighter than me yet doesnt have skin issues remotely as bad as mine.


Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes.
Schmuth M, Haqq CM, Cairns WJ, Holder JC, Dorsam S, Chang S, Lau P, Fowler AJ, Chuang G, Moser AH, Brown BE, Mao-Qiang M, Uchida Y, Schoonjans K, Auwerx J, Chambon P, Willson TM, Elias PM, Feingold KR.

Department of Medicine, University of California, San Francisco, California, USA.
Erratum in:

J Invest Dermatol. 2004 Oct;123(4):806.
Peroxisome proliferator-activated receptor (PPAR) are nuclear hormone receptors that are activated by endogenous lipid metabolites. Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier homeostasis. Recent studies have shown that PPAR-beta/delta activation induces keratinocyte differentiation in vitro. This study demonstrated that topical treatment of mice with a selective PPAR-beta/delta agonist (GW1514) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation [corrected]. In contrast to PPAR-alpha activation, PPAR-beta/deltain vivo did not display anti-proliferative or pro-apoptotic effects. The pro-differentiating effects persisted in mice lacking PPAR-alpha, but were decreased in mice deficient in retinoid X receptor-alpha, the major heterodimerization partner of PPAR. Furthermore, in vitro PPAR-beta/delta activation, aside from stimulating differentiation-related genes, additionally induced adipose differentiation-related protein (ADRP) and fasting induced adipose factor (FIAF) mRNA in cultures keratinocytes, which was paralleled by increased oil red O staining indicative of lipid accumulation, the bulk of which were triglycerides (TG). Comparison of differentially expressed genes between PPAR-beta/delta and PPAR-alpha activation revealed distinct profiles. Together, these studies indicate that PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates TG accumulation in keratinocytes.
i think that you can find something herbal that works the same way.i suggest supplementation as topical works only as long as you use the product.i found this link that says that Pomegranate Juice Extract May Help Prevent or Control Diabetes[/url] via ppar stimulation
 
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