Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α (3 views)
Pharmaceutics (ISSN: 1999-4923linking, 1999-4923electronic), 2022 Jan 31; 14(2): N/D-N/D.
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Paper type: Journal Article
Impact factor: 6.321, 5-year impact factor: 0
Url: Not available.
Keywords: Adipocyte Remodeling, Beige Adipocytes, Brown And White Adipose Tissue, Human Adipose Stromal Cells, Leptin Signaling, Peroxisome Proliferator-Activated Receptor-A
Affiliations:
*** IBB - CNR ***
Department of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, Italy.
Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60020 Ancona, Italy.
Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, 04100 Latina, Italy.
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy.
Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy.
Institute of Biostructure and Bioimaging, National Research Council (CNR), 80134 Naples, Italy.
Department of Biology, University of Naples Federico II, 80126 Naples, Italy.
Mediterranea Cardiocenter, 80122 Naples, Italy.
References:
Not available.
Pharmaceutics (ISSN: 1999-4923linking, 1999-4923electronic), 2022 Jan 31; 14(2): N/D-N/D.
Export to BibTeX Export to EndNote
Paper type: Journal Article
Impact factor: 6.321, 5-year impact factor: 0
Url: Not available.
Keywords: Adipocyte Remodeling, Beige Adipocytes, Brown And White Adipose Tissue, Human Adipose Stromal Cells, Leptin Signaling, Peroxisome Proliferator-Activated Receptor-A
Affiliations:
*** IBB - CNR ***
Department of Pharmacy, School of Medicine, University of Naples Federico II, 80131 Naples, Italy.
Department of Experimental and Clinical Medicine, Marche Polytechnic University, 60020 Ancona, Italy.
Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, 04100 Latina, Italy.
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy.
Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy.
Institute of Biostructure and Bioimaging, National Research Council (CNR), 80134 Naples, Italy.
Department of Biology, University of Naples Federico II, 80126 Naples, Italy.
Mediterranea Cardiocenter, 80122 Naples, Italy.
References:
Not available.
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 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.
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.
Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α
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