Related Experiment Video
Updated: Aug 20, 2025
Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells
Published on: March 28, 2013
A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist
Federica Papaccio1, Barbara Bellei1, Monica Ottaviani1
1Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatological Institute, IRCCS, 00144 Rome, Italy.
Abstract:
Vitiligo is a complex disease wherein derangements in multiple pathways determine the loss of functional melanocytes. Since its pathogenesis is not yet completely understood, vitiligo lacks a definitive safe and efficacious treatment. At present, different therapies are available; however, each modality has its baggage of disadvantages and side effects. Recently we have described several metabolic abnormalities in cells from pigmented skin of vitiligo patients, including alterations of glucose metabolism. Therefore, we conducted a study to evaluate the effect of Pioglitazone (PGZ), a Peroxisome proliferator-activated receptor-γ (PPARγ) agonist, on cells from pigmented vitiligo skin. We treated vitiligo melanocytes and fibroblasts with low doses of PGZ and evaluated the effects on mitochondrial alterations, previously reported by our and other groups. Treatment with PGZ significantly increased mRNA and protein levels of several anaerobic glycolytic enzymes, without increasing glucose consumption. The PGZ administration fully restored the metabolic network, replacing mitochondrial membrane potential and mitochondrial DNA (mtDNA) copy number. These effects, together with a significant increase in ATP content and a decrease in reactive oxygen species (ROS) production, provide strong evidence of an overall improvement of mitochondria bioenergetics in vitiligo cells. Moreover, the expression of HMGB1, Hsp70, defined as a part of DAMPs, and PD-L1 were significantly reduced. In addition, PGZ likely reverts premature senescence phenotype. In summary, the results outline a novel mode of action of Pioglitazone, which may turn out to be relevant to the development of effective new vitiligo therapeutic strategies.
Insights
Pioglitazone (PGZ) treatment improved mitochondrial function in vitiligo cells by restoring metabolic balance and reducing cellular damage. This suggests PGZ may offer a novel therapeutic strategy for vitiligo, a condition lacking effective treatments.
Area of Science:
- Dermatology
- Cell Biology
- Metabolic Research
Background:
- Vitiligo pathogenesis involves complex pathways leading to melanocyte loss, with current treatments having limitations.
- Metabolic abnormalities, including altered glucose metabolism, have been identified in vitiligo patient cells.
- Pioglitazone (PGZ), a PPARγ agonist, was investigated for its effects on vitiligo cells.
Purpose of the Study:
- To evaluate the therapeutic potential of Pioglitazone (PGZ) on cells from pigmented vitiligo skin.
- To investigate PGZ's impact on mitochondrial function and metabolic pathways in vitiligo.
- To assess PGZ's effects on senescence markers and inflammatory signals in vitiligo cells.
Main Methods:
- Vitiligo melanocytes and fibroblasts were treated with low-dose Pioglitazone (PGZ).
- Effects on mitochondrial alterations, mRNA and protein levels of glycolytic enzymes, glucose consumption, and ATP content were evaluated.
- Changes in mitochondrial membrane potential, mtDNA copy number, reactive oxygen species (ROS) production, and expression of HMGB1, Hsp70, and PD-L1 were assessed.
Main Results:
- PGZ treatment increased anaerobic glycolytic enzymes without affecting glucose consumption.
- PGZ restored mitochondrial membrane potential and mtDNA copy number, enhancing mitochondrial bioenergetics.
- PGZ significantly reduced HMGB1, Hsp70, and PD-L1 expression, and appeared to reverse premature senescence.
Conclusions:
- Pioglitazone (PGZ) demonstrates a novel mode of action by improving mitochondrial bioenergetics and reducing inflammatory markers in vitiligo cells.
- These findings suggest Pioglitazone (PGZ) holds promise as a potential therapeutic agent for vitiligo.
- Further research into PGZ's efficacy could lead to new treatment strategies for vitiligo.
More Related Videos
Related Concept Videos
01:23Role of Skin in Vitamin D Synthesis
The solar UV B rays (290-315 nm) are absorbed by the skin, and 7-dehydrocholesterol (provitamin D3) photolyzes it to previtamin D3, which undergoes a rapid transformation to vitamin...
01:19Regulation of Metabolism
01:26Oral Hypoglycemic Agents: Biguanides and Glitazones