Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α
The potential role of brown and beige adipose tissue against obesity has been recognized. Browning, or beiging of white adipose tissue (WAT) is associated with the remodeling of adipocytes and the improvement of their metabolic and secretory functions. Here, palmitoylethanolamide (PEA) restore the p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/2/338 |
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| author | Chiara Annunziata Claudio Pirozzi Adriano Lama Martina Senzacqua Federica Comella Antonella Bordin Anna Monnolo Alessandra Pelagalli Maria Carmela Ferrante Maria Pina Mollica Angelo Iossa Elena De Falco Giuseppina Mattace Raso Saverio Cinti Antonio Giordano Rosaria Meli |
| author_facet | Chiara Annunziata Claudio Pirozzi Adriano Lama Martina Senzacqua Federica Comella Antonella Bordin Anna Monnolo Alessandra Pelagalli Maria Carmela Ferrante Maria Pina Mollica Angelo Iossa Elena De Falco Giuseppina Mattace Raso Saverio Cinti Antonio Giordano Rosaria Meli |
| author_sort | Chiara Annunziata |
| collection | DOAJ |
| description | The potential role of brown and beige adipose tissue against obesity has been recognized. Browning, or beiging of white adipose tissue (WAT) is associated with the remodeling of adipocytes and the improvement of their metabolic and secretory functions. Here, palmitoylethanolamide (PEA) restore the plasticity of brown and white adipocytes impaired in mice on a high-fat diet (HFD). Young male C57Bl/6J mice were fed with control (STD) diet or HFD for 12 weeks. Ultramicronized PEA (30 mg/kg/die p.o.) was administered for an additional 7 weeks, together with HFD. PEA recovered interscapular brown fat morphology and function, increasing UCP1 positivity, noradrenergic innervation, and inducing the mRNA transcription of several specialized thermogenic genes. PEA promotes the beige-conversion of the subcutaneous WAT, increasing thermogenic markers and restoring leptin signaling and tissue hormone sensitivity. The pivotal role of lipid-sensing peroxisome proliferator-activated receptor (PPAR)-α in PEA effects was determined in mature 3T3-L1. Moreover, PEA improved mitochondrial bioenergetics in mature adipocytes measured by a Seahorse analyzer and induced metabolic machinery via AMPK phosphorylation. All these outcomes were dampened by the receptor antagonist GW6471. Finally, PEA induced adipogenic differentiation and increased AMPK phosphorylation in human adipose-derived stromal cells (ASCs) obtained from subcutaneous WAT of normal-weight patients and patients with obesity. We identify PEA and PPAR-α activation as the main mechanism by which PEA can rewire energy-storing white into energy-consuming brown-like adipocytes via multiple and converging effects that restore WAT homeostasis and metabolic flexibility. |
| first_indexed | 2024-03-09T21:15:22Z |
| format | Article |
| id | doaj.art-d69c37519670409d9c524e04a39b1030 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T21:15:22Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d69c37519670409d9c524e04a39b10302023-11-23T21:37:38ZengMDPI AGPharmaceutics1999-49232022-01-0114233810.3390/pharmaceutics14020338Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-αChiara Annunziata0Claudio Pirozzi1Adriano Lama2Martina Senzacqua3Federica Comella4Antonella Bordin5Anna Monnolo6Alessandra Pelagalli7Maria Carmela Ferrante8Maria Pina Mollica9Angelo Iossa10Elena De Falco11Giuseppina Mattace Raso12Saverio Cinti13Antonio Giordano14Rosaria Meli15Department of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyDepartment of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyDepartment of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyDepartment of Experimental and Clinical Medicine, Marche Polytechnic University, 60020 Ancona, ItalyDepartment of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyDepartment of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, 04100 Latina, ItalyDepartment of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, ItalyDepartment of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, ItalyDepartment of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, ItalyDepartment of Biology, University of Naples Federico II, 80126 Naples, ItalyDepartment of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, 04100 Latina, ItalyDepartment of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, 04100 Latina, ItalyDepartment of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyDepartment of Experimental and Clinical Medicine, Marche Polytechnic University, 60020 Ancona, ItalyDepartment of Experimental and Clinical Medicine, Marche Polytechnic University, 60020 Ancona, ItalyDepartment of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, ItalyThe potential role of brown and beige adipose tissue against obesity has been recognized. Browning, or beiging of white adipose tissue (WAT) is associated with the remodeling of adipocytes and the improvement of their metabolic and secretory functions. Here, palmitoylethanolamide (PEA) restore the plasticity of brown and white adipocytes impaired in mice on a high-fat diet (HFD). Young male C57Bl/6J mice were fed with control (STD) diet or HFD for 12 weeks. Ultramicronized PEA (30 mg/kg/die p.o.) was administered for an additional 7 weeks, together with HFD. PEA recovered interscapular brown fat morphology and function, increasing UCP1 positivity, noradrenergic innervation, and inducing the mRNA transcription of several specialized thermogenic genes. PEA promotes the beige-conversion of the subcutaneous WAT, increasing thermogenic markers and restoring leptin signaling and tissue hormone sensitivity. The pivotal role of lipid-sensing peroxisome proliferator-activated receptor (PPAR)-α in PEA effects was determined in mature 3T3-L1. Moreover, PEA improved mitochondrial bioenergetics in mature adipocytes measured by a Seahorse analyzer and induced metabolic machinery via AMPK phosphorylation. All these outcomes were dampened by the receptor antagonist GW6471. Finally, PEA induced adipogenic differentiation and increased AMPK phosphorylation in human adipose-derived stromal cells (ASCs) obtained from subcutaneous WAT of normal-weight patients and patients with obesity. We identify PEA and PPAR-α activation as the main mechanism by which PEA can rewire energy-storing white into energy-consuming brown-like adipocytes via multiple and converging effects that restore WAT homeostasis and metabolic flexibility.https://www.mdpi.com/1999-4923/14/2/338brown and white adipose tissuebeige adipocytesadipocyte remodelingperoxisome proliferator-activated receptor-aleptin signalinghuman adipose stromal cells |
| spellingShingle | Chiara Annunziata Claudio Pirozzi Adriano Lama Martina Senzacqua Federica Comella Antonella Bordin Anna Monnolo Alessandra Pelagalli Maria Carmela Ferrante Maria Pina Mollica Angelo Iossa Elena De Falco Giuseppina Mattace Raso Saverio Cinti Antonio Giordano Rosaria Meli Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α Pharmaceutics brown and white adipose tissue beige adipocytes adipocyte remodeling peroxisome proliferator-activated receptor-a leptin signaling human adipose stromal cells |
| title | Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α |
| title_full | Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α |
| title_fullStr | Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α |
| title_full_unstemmed | Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α |
| title_short | Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α |
| title_sort | palmitoylethanolamide promotes white to beige conversion and metabolic reprogramming of adipocytes contribution of ppar α |
| topic | brown and white adipose tissue beige adipocytes adipocyte remodeling peroxisome proliferator-activated receptor-a leptin signaling human adipose stromal cells |
| url | https://www.mdpi.com/1999-4923/14/2/338 |
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