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Indomethacin promotes browning and brown adipogenesis in both murine and human fat cells

Indomethacin (Indo), a nonsteroidal antiinflammatory drug, has been shown to promote murine brown adipogenesis both in vitro and in vivo, possibly due to its peroxisome proliferator‐activated receptor gamma (PPARγ)‐agonist activities. However, it is unclear whether Indo induces browning of white adi...

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Autores principales: Overby, Haley, Yang, Yang, Xu, Xinyun, Wang, Shu, Zhao, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237299/
https://www.ncbi.nlm.nih.gov/pubmed/32430973
http://dx.doi.org/10.1002/prp2.592
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author Overby, Haley
Yang, Yang
Xu, Xinyun
Wang, Shu
Zhao, Ling
author_facet Overby, Haley
Yang, Yang
Xu, Xinyun
Wang, Shu
Zhao, Ling
author_sort Overby, Haley
collection PubMed
description Indomethacin (Indo), a nonsteroidal antiinflammatory drug, has been shown to promote murine brown adipogenesis both in vitro and in vivo, possibly due to its peroxisome proliferator‐activated receptor gamma (PPARγ)‐agonist activities. However, it is unclear whether Indo induces browning of white adipocytes from both murine and human origins or induces human brown adipogenesis. To bridge the gap, this study investigated the effects of increasing concentrations of Indo on murine 3T3‐L1, human primary subcutaneous white adipocytes (HPsubQ), and human brown (HBr) adipocytes. The results show that Indo dose‐dependently enhanced 3T3‐L1 adipocyte differentiation and upregulated both mRNA and protein expression of brown and beige adipocyte markers, while simultaneously suppressing white adipocyte‐specific marker mRNA expression. mRNA and protein expression of mitochondrial biogenesis and structural genes were dose‐dependently enhanced in Indo treated 3T3‐L1 adipocytes. This was accompanied by augmented mitochondrial DNA, enhanced oxygen consumption, proton leak, and maximal and spare respiratory capacity. Dose‐dependent transactivation of PPARγ confirmed Indo's PPARγ‐agonist activity in 3T3‐L1 cells. Knockdown of PPARγ significantly attenuated Indo's activities in selective browning genes, demonstrating PPARγ dependence of these effects. Moreover, Indo enhanced mRNA and protein expression of brown markers in HPsubQ adipocytes. Interestingly, Indo‐induced differential effects on individual PPARγ isoforms with significant dose‐dependent induction of PPARγ‐2 and suppression of PPARγ‐1 protein expression. Finally, Indo significantly promoted brown adipogenesis in HBr cells. Taken together, these results demonstrate Indo to be a potent thermogenic compound in both murine and human fat cells and may be explored as a therapeutic agent for obesity treatment and prevention.
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spelling pubmed-72372992020-05-21 Indomethacin promotes browning and brown adipogenesis in both murine and human fat cells Overby, Haley Yang, Yang Xu, Xinyun Wang, Shu Zhao, Ling Pharmacol Res Perspect Original Articles Indomethacin (Indo), a nonsteroidal antiinflammatory drug, has been shown to promote murine brown adipogenesis both in vitro and in vivo, possibly due to its peroxisome proliferator‐activated receptor gamma (PPARγ)‐agonist activities. However, it is unclear whether Indo induces browning of white adipocytes from both murine and human origins or induces human brown adipogenesis. To bridge the gap, this study investigated the effects of increasing concentrations of Indo on murine 3T3‐L1, human primary subcutaneous white adipocytes (HPsubQ), and human brown (HBr) adipocytes. The results show that Indo dose‐dependently enhanced 3T3‐L1 adipocyte differentiation and upregulated both mRNA and protein expression of brown and beige adipocyte markers, while simultaneously suppressing white adipocyte‐specific marker mRNA expression. mRNA and protein expression of mitochondrial biogenesis and structural genes were dose‐dependently enhanced in Indo treated 3T3‐L1 adipocytes. This was accompanied by augmented mitochondrial DNA, enhanced oxygen consumption, proton leak, and maximal and spare respiratory capacity. Dose‐dependent transactivation of PPARγ confirmed Indo's PPARγ‐agonist activity in 3T3‐L1 cells. Knockdown of PPARγ significantly attenuated Indo's activities in selective browning genes, demonstrating PPARγ dependence of these effects. Moreover, Indo enhanced mRNA and protein expression of brown markers in HPsubQ adipocytes. Interestingly, Indo‐induced differential effects on individual PPARγ isoforms with significant dose‐dependent induction of PPARγ‐2 and suppression of PPARγ‐1 protein expression. Finally, Indo significantly promoted brown adipogenesis in HBr cells. Taken together, these results demonstrate Indo to be a potent thermogenic compound in both murine and human fat cells and may be explored as a therapeutic agent for obesity treatment and prevention. John Wiley and Sons Inc. 2020-05-19 /pmc/articles/PMC7237299/ /pubmed/32430973 http://dx.doi.org/10.1002/prp2.592 Text en © 2020 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Overby, Haley
Yang, Yang
Xu, Xinyun
Wang, Shu
Zhao, Ling
Indomethacin promotes browning and brown adipogenesis in both murine and human fat cells
title Indomethacin promotes browning and brown adipogenesis in both murine and human fat cells
title_full Indomethacin promotes browning and brown adipogenesis in both murine and human fat cells
title_fullStr Indomethacin promotes browning and brown adipogenesis in both murine and human fat cells
title_full_unstemmed Indomethacin promotes browning and brown adipogenesis in both murine and human fat cells
title_short Indomethacin promotes browning and brown adipogenesis in both murine and human fat cells
title_sort indomethacin promotes browning and brown adipogenesis in both murine and human fat cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237299/
https://www.ncbi.nlm.nih.gov/pubmed/32430973
http://dx.doi.org/10.1002/prp2.592
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