Progressive Expression Of Ppargc1α Is Associated With Hair Miniaturization In Androgenetic Alopecia

[whatevr]

https://www.nature.com/articles/s41598-019-43998-7

Current opinion views androgens as the pathogenic driver in the miniaturization of hair follicles of androgenetic alopecia by interfering with the dermal papilla. This cannot be the sole cause and therefore it is important for therapeutic and diagnostic purposes to identify additional pathways. Comparative full transcriptome profile analysis of the hair bulb region of normal and miniaturized hair follicles from vertex and occipital region in males with and without androgenetic alopecia revealed that next to the androgen receptor as well the retinoid receptor and particularly the PPAR pathway is involved in progressive hair miniaturization. We demonstrate the concurrent up-regulation of PPARGC1a in the epithelial compartment and androgen receptor in the dermal papilla of miniaturized hair. Dynamic Ppargc1a expression in the mouse hair cycle suggests a possible role in regulating hair growth and differentiation. This is supported by reduced proliferation of human dermal papilla and predominantly epithelial keratinocytes after incubation with AICAR, the agonist for AMPK signaling which activates PPARGC1a and serves as co-activator of PPARγ. In addition, miRNA profiling shows enrichment of miRNA-targeted genes in retinoid receptors and PPARGC1α/PPARγ signaling, and antigen presentation pathways.

 

[whatevr]

Interestingly enough, in a study posted by another member, AMPK agonist AICAR is claimed to promote hair growth:

https://www.sciencedirect.com/science/article/pii/S2211124719306990

However, in this study, AICAR is responsible for the activation of PPARGC1a which the authors claim is associated with miniaturization (in this case, associated merely means they found it upregulated wherever there is miniaturization). Given the above, it is possible that the PPAR upregulation is a protective, rather than causative one. Even the authors of the original study note this:

"Further work needs to be done to distinguish if PGC1a is involved in Androgenetic Alopecia pathogenesis or plays a protective role against Androgenetic Alopecia."

 

[pegasus2]

Interestingly enough, in a study posted by another member, AMPK agonist AICAR is claimed to promote hair growth:

https://www.sciencedirect.com/science/article/pii/S2211124719306990

However, in this study, AICAR is responsible for the activation of PPARGC1a which the authors claim is associated with miniaturization (in this case, associated merely means they found it upregulated wherever there is miniaturization). Given the above, it is possible that the PPAR upregulation is a protective, rather than causative one. Even the authors of the original study note this:

"Further work needs to be done to distinguish if PGC1a is involved in Androgenetic Alopecia pathogenesis or plays a protective role against Androgenetic Alopecia."

Interestingly enough, in a study posted by another member, AMPK agonist AICAR is claimed to promote hair growth:

https://www.sciencedirect.com/science/article/pii/S2211124719306990

However, in this study, AICAR is responsible for the activation of PPARGC1a which the authors claim is associated with miniaturization (in this case, associated merely means they found it upregulated wherever there is miniaturization). Given the above, it is possible that the PPAR upregulation is a protective, rather than causative one. Even the authors of the original study note this:

"Further work needs to be done to distinguish if PGC1a is involved in Androgenetic Alopecia pathogenesis or plays a protective role against Androgenetic Alopecia."

This is what I've been thinking, and take a look at this study.
https://onlinelibrary.wiley.com/doi/full/10.1111/exd.14062

PPARγ is anti-fibrotic, it inhibits TGF-β, and its deletion results in scarring alopecia.

Its effects on HF modulation may be dose-dependent

Reportedly, human HF growth ex vivo can even be stimulated by low concentrations of a specific PPAR‐α agonist, but inhibited by high concentrations of the same modulator,59 suggesting that the targeted PPAR isoform(s), signalling pathways and primary target genes of these endogenous ligands also are dose‐dependent.

Full agonists may not work, however mineralocorticoid receptor antagonists can be used to normalize PPARγ.

 

[DavidsDome]

Dont we need a PPAR antagonist in stead of an agonist?
Although the scarring alopecia is worrying...

Betulinic acid is a PPARγ antagonist that improves glucose uptake, promotes osteogenesis and inhibits adipogenesis
...we identified betulinic acid (BA), a compound already known for its anti-inflammatory, anti-tumour and antidiabetic properties, as a PPARγ and PPARα antagonist...

Betulinic acid is a PPARγ antagonist that improves glucose uptake, promotes osteogenesis and inhibits adipogenesis

PPAR antagonists are ligands that bind their receptor with high affinity without transactivation activity. Recently, they have been demonstrated to maintain insulin-sensitizing and antidiabetic properties, and they serve as an alternative treatment for ...

www.ncbi.nlm.nih.gov

Betulin creme is available for psoriasis sufferers.
It's also claimed to improve wound healing.