Understanding Peroxisome Proliferator-Activated Receptors: From the Structure to the Regulatory Actions on Metabolism

Bervejillo, María Lamas; Ferreira, Ana Maria da Costa

doi:10.1007/978-3-030-11488-6_3

Cited by 24 publications

(18 citation statements)

References 94 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%

“…PPARs are nuclear hormone receptors abundantly expressed in tissues that display high fatty acid metabolism, including human skin and its appendages . Three different isoforms of PPARs exist—PPAR‐α, PPAR‐β/δ and PPAR‐γ, which demonstrate diverse functional capabilities, including—to name but a few examples—the control of lipogenesis, cell cycle and inflammatory gene expression (Figure ) …”

Section: Ppars In Human Biology and Skinmentioning

confidence: 99%

“…control of lipogenesis, cell cycle and inflammatory gene expression ( Figure 1). [4,5,39,40] PPARs are transcription factors that regulate gene transcription either negatively or positively. They are activated by binding of specific ligands or by kinase-mediated phosphorylation.…”

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confidence: 99%

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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%

Section: Ppars In Human Biology and Skinmentioning

confidence: 99%

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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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“… 139 , 140 Structurally, PPARs contain an N-terminal transactivating domain, a highly conserved DNA-binding domain that recognizes PPAR-specific DNA binding domains, or PPAR-response elements (PPREs), and a C-terminal ligand-binding domain. 141 , 142 Ligand binding to PPARs facilitates heterodimerization with the retinoid-X-receptor (RXR), binding to PPREs, a six nucleotide dimeric repeat separated by a single nucleotide (AGGTCA-N-AGGTCA), and activation of transcription. 141 , 142 Of note, the binding pocket of PPARs is relatively large compared to other nuclear receptors, facilitating binding of endogenous FAs and greater overall flexibility in ligand binding.…”

Section: Peroxisome Proliferator-activated Receptorsmentioning

confidence: 99%

“… 141 , 142 Ligand binding to PPARs facilitates heterodimerization with the retinoid-X-receptor (RXR), binding to PPREs, a six nucleotide dimeric repeat separated by a single nucleotide (AGGTCA-N-AGGTCA), and activation of transcription. 141 , 142 Of note, the binding pocket of PPARs is relatively large compared to other nuclear receptors, facilitating binding of endogenous FAs and greater overall flexibility in ligand binding.…”

Section: Peroxisome Proliferator-activated Receptorsmentioning

confidence: 99%

Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites

OʼConnell

Mason

Budoff

et al. 2020

European Heart Journal Supplements

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Patients with well-controlled low-density lipoprotein cholesterol levels, but persistent high triglycerides, remain at increased risk for cardiovascular events as evidenced by multiple genetic and epidemiologic studies, as well as recent clinical outcome trials. While many trials of low-dose ω3-polyunsaturated fatty acids (ω3-PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have shown mixed results to reduce cardiovascular events, recent trials with high-dose ω3-PUFAs have reignited interest in ω3-PUFAs, particularly EPA, in cardiovascular disease (CVD). REDUCE-IT demonstrated that high-dose EPA (4 g/day icosapent-ethyl) reduced a composite of clinical events by 25% in statin-treated patients with established CVD or diabetes and other cardiovascular risk factors. Outcome trials in similar statin-treated patients using DHA-containing high-dose ω3 formulations have not yet shown the benefits of EPA alone. However, there are data to show that high-dose ω3-PUFAs in patients with acute myocardial infarction had reduced left ventricular remodelling, non-infarct myocardial fibrosis, and systemic inflammation. ω3-polyunsaturated fatty acids, along with their metabolites, such as oxylipins and other lipid mediators, have complex effects on the cardiovascular system. Together they target free fatty acid receptors and peroxisome proliferator-activated receptors in various tissues to modulate inflammation and lipid metabolism. Here, we review these multifactorial mechanisms of ω3-PUFAs in view of recent clinical findings. These findings indicate physico-chemical and biological diversity among ω3-PUFAs that influence tissue distributions as well as disparate effects on membrane organization, rates of lipid oxidation, as well as various receptor-mediated signal transduction pathways and effects on gene expression.

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Perfluorooctanesulfonic Acid–Induced Toxicity on Zebrafish Embryos in the Presence or Absence of the Chorion

Mylroie

Wilbanks

Kimble

et al. 2020

Enviro Toxic and Chemistry

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Perfluorooctanesulfonic acid (PFOS) is a perfluorinated compound used in many industrial and consumer products. It has been linked to a broad range of adverse effects in several species, including zebrafish (Danio rerio). The zebrafish embryo is a widely used vertebrate model to elucidate potential adverse effects of chemicals because it is amenable to medium and high throughput. However, there is limited research on the full extent of the impact the chorion has on those effects. Results from the present study indicate that the presence of the chorion affected the timing and incidence of mortality as well as morphometric endpoints such as spinal curvature and swim bladder inflation in zebrafish embryos exposed to PFOS. Furthermore, removal of the chorion prior to exposure resulted in a lower threshold of sensitivity to PFOS for effects on transcriptional expression within the peroxisome proliferator–activated receptor (PPAR) nuclear signaling pathway. Perturbation of PPAR pathway gene expression can result in disruption of metabolic signaling and regulation, which can adversely affect development, energy availability, and survival. It can be concluded that removal of the chorion has significant effects on the timing and incidence of impacts associated with PFOS exposure, and more research is warranted to fully elucidate the protective role of the chorion and the critical timing of these events. Environ Toxicol Chem 2021;40:780–791. Published 2020. This article is a US Government work and is in the public domain in the USA. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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Understanding Peroxisome Proliferator-Activated Receptors: From the Structure to the Regulatory Actions on Metabolism

Cited by 24 publications

References 94 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

Mechanistic insights into cardiovascular protection for omega-3 fatty acids and their bioactive lipid metabolites

Perfluorooctanesulfonic Acid–Induced Toxicity on Zebrafish Embryos in the Presence or Absence of the Chorion

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