Cargando…

Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma

Identifying functional brown adipose tissue (BAT) has provided new hope for obesity treatment and prevention. Functional BAT includes classical BAT and brown-like adipose tissue converted from white adipose tissue. By promoting thermogenesis (i.e., heat production) via uncoupling protein 1 (UCP1), f...

Descripción completa

Detalles Bibliográficos
Autores principales: Bae, Jiyoung, Yang, Yang, Xu, Xinyun, Flaherty, Jamie, Overby, Haley, Hildreth, Kelsey, Chen, Jiangang, Wang, Shu, Zhao, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686290/
https://www.ncbi.nlm.nih.gov/pubmed/36438760
http://dx.doi.org/10.3389/fnut.2022.1036655
_version_ 1784835711775539200
author Bae, Jiyoung
Yang, Yang
Xu, Xinyun
Flaherty, Jamie
Overby, Haley
Hildreth, Kelsey
Chen, Jiangang
Wang, Shu
Zhao, Ling
author_facet Bae, Jiyoung
Yang, Yang
Xu, Xinyun
Flaherty, Jamie
Overby, Haley
Hildreth, Kelsey
Chen, Jiangang
Wang, Shu
Zhao, Ling
author_sort Bae, Jiyoung
collection PubMed
description Identifying functional brown adipose tissue (BAT) has provided new hope for obesity treatment and prevention. Functional BAT includes classical BAT and brown-like adipose tissue converted from white adipose tissue. By promoting thermogenesis (i.e., heat production) via uncoupling protein 1 (UCP1), functional BAT can increase energy expenditure and aid obesity treatment and prevention. Naringenin (NAR) is a flavanone primarily found in citrus fruits. NAR has been reported to decrease body weight, increase energy expenditure in treated mice, and promote browning in human adipocytes. Here, we examined the effects of NAR on 3T3-L1 adipocytes’ browning and β-adrenergic agonist isoproterenol (ISO)-stimulated thermogenic activation and classical murine brown adipogenesis. In addition, we demonstrated the signaling pathways and involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in the process. We found that NAR did not increase Ucp1 mRNA expression at the basal (i.e., non-ISO stimulated) condition. Instead, it enhanced Ucp1 and Pgc-1α up-regulation and thermogenesis under ISO-stimulated conditions in 3T3-L1 adipocytes. NAR promoted protein kinase A (PKA) activation and phosphorylation of p38 MAPK downstream of ISO stimulation and activated PPARγ. Pharmacological inhibition of either PKA or p38 and PPARγ knockdown attenuated Ucp1 up-regulation by NAR. Moreover, NAR promoted brown adipogenesis by increasing lipid accumulation, brown marker expression, and thermogenesis in murine brown adipocytes, which was also attenuated by PPARγ knockdown. Together, our results suggest that NAR may promote the development of functional BAT in part through PPARγ activation. NAR’s role in combating human obesity warrants further investigation.
format Online
Article
Text
id pubmed-9686290
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-96862902022-11-25 Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma Bae, Jiyoung Yang, Yang Xu, Xinyun Flaherty, Jamie Overby, Haley Hildreth, Kelsey Chen, Jiangang Wang, Shu Zhao, Ling Front Nutr Nutrition Identifying functional brown adipose tissue (BAT) has provided new hope for obesity treatment and prevention. Functional BAT includes classical BAT and brown-like adipose tissue converted from white adipose tissue. By promoting thermogenesis (i.e., heat production) via uncoupling protein 1 (UCP1), functional BAT can increase energy expenditure and aid obesity treatment and prevention. Naringenin (NAR) is a flavanone primarily found in citrus fruits. NAR has been reported to decrease body weight, increase energy expenditure in treated mice, and promote browning in human adipocytes. Here, we examined the effects of NAR on 3T3-L1 adipocytes’ browning and β-adrenergic agonist isoproterenol (ISO)-stimulated thermogenic activation and classical murine brown adipogenesis. In addition, we demonstrated the signaling pathways and involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in the process. We found that NAR did not increase Ucp1 mRNA expression at the basal (i.e., non-ISO stimulated) condition. Instead, it enhanced Ucp1 and Pgc-1α up-regulation and thermogenesis under ISO-stimulated conditions in 3T3-L1 adipocytes. NAR promoted protein kinase A (PKA) activation and phosphorylation of p38 MAPK downstream of ISO stimulation and activated PPARγ. Pharmacological inhibition of either PKA or p38 and PPARγ knockdown attenuated Ucp1 up-regulation by NAR. Moreover, NAR promoted brown adipogenesis by increasing lipid accumulation, brown marker expression, and thermogenesis in murine brown adipocytes, which was also attenuated by PPARγ knockdown. Together, our results suggest that NAR may promote the development of functional BAT in part through PPARγ activation. NAR’s role in combating human obesity warrants further investigation. Frontiers Media S.A. 2022-11-10 /pmc/articles/PMC9686290/ /pubmed/36438760 http://dx.doi.org/10.3389/fnut.2022.1036655 Text en Copyright © 2022 Bae, Yang, Xu, Flaherty, Overby, Hildreth, Chen, Wang and Zhao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Bae, Jiyoung
Yang, Yang
Xu, Xinyun
Flaherty, Jamie
Overby, Haley
Hildreth, Kelsey
Chen, Jiangang
Wang, Shu
Zhao, Ling
Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma
title Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma
title_full Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma
title_fullStr Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma
title_full_unstemmed Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma
title_short Naringenin, a citrus flavanone, enhances browning and brown adipogenesis: Role of peroxisome proliferator-activated receptor gamma
title_sort naringenin, a citrus flavanone, enhances browning and brown adipogenesis: role of peroxisome proliferator-activated receptor gamma
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686290/
https://www.ncbi.nlm.nih.gov/pubmed/36438760
http://dx.doi.org/10.3389/fnut.2022.1036655
work_keys_str_mv AT baejiyoung naringeninacitrusflavanoneenhancesbrowningandbrownadipogenesisroleofperoxisomeproliferatoractivatedreceptorgamma
AT yangyang naringeninacitrusflavanoneenhancesbrowningandbrownadipogenesisroleofperoxisomeproliferatoractivatedreceptorgamma
AT xuxinyun naringeninacitrusflavanoneenhancesbrowningandbrownadipogenesisroleofperoxisomeproliferatoractivatedreceptorgamma
AT flahertyjamie naringeninacitrusflavanoneenhancesbrowningandbrownadipogenesisroleofperoxisomeproliferatoractivatedreceptorgamma
AT overbyhaley naringeninacitrusflavanoneenhancesbrowningandbrownadipogenesisroleofperoxisomeproliferatoractivatedreceptorgamma
AT hildrethkelsey naringeninacitrusflavanoneenhancesbrowningandbrownadipogenesisroleofperoxisomeproliferatoractivatedreceptorgamma
AT chenjiangang naringeninacitrusflavanoneenhancesbrowningandbrownadipogenesisroleofperoxisomeproliferatoractivatedreceptorgamma
AT wangshu naringeninacitrusflavanoneenhancesbrowningandbrownadipogenesisroleofperoxisomeproliferatoractivatedreceptorgamma
AT zhaoling naringeninacitrusflavanoneenhancesbrowningandbrownadipogenesisroleofperoxisomeproliferatoractivatedreceptorgamma