Peroxisome Proliferator-Activated Receptor Modulation during Metabolic Diseases and Cancers: Master and Minions

Vitale, Salvatore Giovanni; Laganà, Antonio Simone; Nigro, A.; Rosa, Valentina Lucia La; Rossetti, Paola; Rapisarda, Agnese Maria Chiara; Vignera, Sandro La; Condorelli, Rosita A.; Corrado, Francesco; Buscema, Massimo; D’Anna, Rosario

doi:10.1155/2016/6517313

Cited by 97 publications

(69 citation statements)

References 92 publications

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“…Since their identification as receptors responsible for peroxisome proliferation in 1990, research on peroxisome proliferator‐activated receptors (PPARs) has increased dramatically, revealing more and more fascinating functions in human biology. This research also has revealed that dysregulation of PPARs is connected to the development of a wide range of human diseases, including atherosclerosis, obesity, type 2 diabetes and many others …”

Section: Ppars In Human Biology and Skinmentioning

confidence: 99%

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Ramot

Bertolini

Boboljova

et al. 2019

Experimental Dermatology

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Peroxisome proliferator‐activated receptors (PPARs) are abundantly expressed in human skin, with PPAR‐γ being the most intensively investigated isoform. In various ex vivo and in vivo models, PPAR‐γ‐mediated signalling has recently surfaced as an essential element of hair follicle (HF) development, growth and stem cell biology. Moreover, the availability of novel, topically applicable PPAR‐γ modulators with a favourable toxicological profile has extended the range of potential applications in clinical dermatology. In this review, we synthesize where this field currently stands and sketch promising future research avenues, focussing on the role of PPAR‐γ‐mediated signalling in the biology and pathology of human scalp HFs, with special emphasis on scarring alopecias such as lichen planopilaris and frontal fibrosing alopecia as model human epithelial stem cell diseases. In particular, we discuss whether and how pharmacological modulation of PPAR‐γ signalling may be employed for the management of hair growth disorders, for example, in scarring alopecia (by reducing HF inflammation as well as by promoting the survival and suppressing pathological epithelial‐mesenchymal transition of keratin 15 + epithelial stem cells in the bulge) and in hirsutism/hypertrichosis (by promoting catagen development). Moreover, we explore the potential role of PPAR‐γ in androgenetic alopecia, HF energy metabolism and HF ageing, and consider clinical perspectives that emanate from the limited data available on this so far. As this field of translational human hair research is still in its infancy, many open questions exist, for which we briefly delineate selected experimental approaches that promise to generate instructive answers in the near future.

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Section: Ppars In Human Biology and Skinmentioning

confidence: 99%

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Ramot

Bertolini

Boboljova

et al. 2019

Experimental Dermatology

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“…The anti-inflammatory effect of PPARs is also realized through the effect on the metabolism of lipid mediators (by regulating the oxidative degradation of fatty acids). PPARs are involved in the control of genes responsible for oxidative lipid metabolism (carnitine palmitoyltransferase I (CPT1), pyruvate dehydrogenase lipoamide kinase isozyme 4 mitochondrial (PDK4), CYP4A, and acyl-CoA oxidase 1 (ACOX1)) [65]. Therefore, PPARs are regulators of mitochondrial and peroxisomal β-oxidation, ketogenesis, and bile acid synthesis.…”

Section: Ppar Researchmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

et al. 2020

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The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferatoractivated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

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“…The mechanisms related with the regulation of insulin sensitivity at the ovarian level are not fully elucidated yet. Definitely an important role has been described relative to Peroxisome proliferator-activated receptors (PPARs) (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

MiRNAs Regulating Insulin Sensitivity Are Dysregulated in Polycystic Ovary Syndrome (PCOS) Ovaries and Are Associated With Markers of Inflammation and Insulin Sensitivity

et al. 2019

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Objective: MicroRNAs (miRNAs) are gene expression regulators. Altered miRNA levels are associated with diabetes, insulin resistance, and inflammation. Insulin resistance and inflammation are both features of Polycystic ovary syndrome (PCOS). The aim of this study was first to assess differences in selected miRNAs (miR-146a, miR-155, miR-320, miR-370, miR-486), involved in insulin sensitivity regulation and inflammation, in women with or without PCOS. Second, to investigate relationships among these miRNAs, insulin, High mobility group box 1 (HMGB1), and IL-6 in follicular fluid (FF), serum 17-beta estradiol (E2), and the number of dominant follicles.Methods: Thirty PCOS and thirty-six non-PCOS women undergoing in vitro fertilization were enrolled. RNA from granulosa cells (GC) and FF was extracted and the specific miRNAs were evaluated using qRT-PCR. HMGB1, insulin, and IL-6 in FF, and serum E2 were assayed using specific kits.Results: MiR-146a, miR-155, miR-486 were upregulated and miR-320 and miR-370 were downregulated in GC from the PCOS patients. In FF, miR-146a, miR-155, and miR-486 showed lower levels in PCOS, whereas miR-320 and miR-370 showed an opposite trend but no significant changes were observed. These miRNAs showed relationships with Body Mass Index (BMI), age, E2, number of dominant follicles, insulin, and HMGB1. Conclusion:In conclusion, the miRNAs analyzed showed changes in PCOS ovaries and had relationships with indices of inflammation and insulin sensitivity within the ovary, providing evidence for new regulatory mechanisms.

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Peroxisome Proliferator-Activated Receptor Modulation during Metabolic Diseases and Cancers: Master and Minions

Cited by 97 publications

References 92 publications

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

MiRNAs Regulating Insulin Sensitivity Are Dysregulated in Polycystic Ovary Syndrome (PCOS) Ovaries and Are Associated With Markers of Inflammation and Insulin Sensitivity

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