Roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor γ, in lean and obese adipocytes

We recently discovered a novel signaling pathway involving activin receptor-like kinase 7 (ALK7), one of the type I transforming growth factor-β receptors. ALK7 and activated Smads 2, 3, and 4 inhibit the master regulators of adipogenesis, CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome pro...

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Autores principales: Yogosawa, Satomi, Izumi, Tetsuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774700/
https://www.ncbi.nlm.nih.gov/pubmed/24052900
http://dx.doi.org/10.4161/adip.24974
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author Yogosawa, Satomi
Izumi, Tetsuro
author_facet Yogosawa, Satomi
Izumi, Tetsuro
author_sort Yogosawa, Satomi
collection PubMed
description We recently discovered a novel signaling pathway involving activin receptor-like kinase 7 (ALK7), one of the type I transforming growth factor-β receptors. ALK7 and activated Smads 2, 3, and 4 inhibit the master regulators of adipogenesis, CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) specifically in differentiated adipocytes, but surprisingly increase both the adipocyte size and lipid content by suppressing lipolysis. Here, we show that, although both transcription factors are suppressed by ALK7 in either the obese or lean state, PPARγ, but not C/EBPα, is further suppressed under obesity through an ALK7-independent pathway. As a result, PPARγ and adipose lipolytic activities are severely downregulated in obesity. Reactivation of PPARγ by ALK7 inactivation leads to downregulation of inflammatory adipocytokines and upregulation of adiponectin. We propose that PPARγ promotes lipid turnover and remodeling by stimulating both triglyceride synthesis and breakdown in differentiated adipocytes. Finally, we discuss the physiological and evolutionary roles of the ALK7-signaling pathway and consider it as a potential target of therapy for obesity.
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spelling pubmed-37747002013-09-19 Roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor γ, in lean and obese adipocytes Yogosawa, Satomi Izumi, Tetsuro Adipocyte Brief Report We recently discovered a novel signaling pathway involving activin receptor-like kinase 7 (ALK7), one of the type I transforming growth factor-β receptors. ALK7 and activated Smads 2, 3, and 4 inhibit the master regulators of adipogenesis, CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) specifically in differentiated adipocytes, but surprisingly increase both the adipocyte size and lipid content by suppressing lipolysis. Here, we show that, although both transcription factors are suppressed by ALK7 in either the obese or lean state, PPARγ, but not C/EBPα, is further suppressed under obesity through an ALK7-independent pathway. As a result, PPARγ and adipose lipolytic activities are severely downregulated in obesity. Reactivation of PPARγ by ALK7 inactivation leads to downregulation of inflammatory adipocytokines and upregulation of adiponectin. We propose that PPARγ promotes lipid turnover and remodeling by stimulating both triglyceride synthesis and breakdown in differentiated adipocytes. Finally, we discuss the physiological and evolutionary roles of the ALK7-signaling pathway and consider it as a potential target of therapy for obesity. Landes Bioscience 2013-10-01 2013-05-13 /pmc/articles/PMC3774700/ /pubmed/24052900 http://dx.doi.org/10.4161/adip.24974 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Brief Report
Yogosawa, Satomi
Izumi, Tetsuro
Roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor γ, in lean and obese adipocytes
title Roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor γ, in lean and obese adipocytes
title_full Roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor γ, in lean and obese adipocytes
title_fullStr Roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor γ, in lean and obese adipocytes
title_full_unstemmed Roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor γ, in lean and obese adipocytes
title_short Roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor γ, in lean and obese adipocytes
title_sort roles of activin receptor-like kinase 7 signaling and its target, peroxisome proliferator-activated receptor γ, in lean and obese adipocytes
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3774700/
https://www.ncbi.nlm.nih.gov/pubmed/24052900
http://dx.doi.org/10.4161/adip.24974
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