Dysfunction of insulin-AKT-UCP1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown-like adipocytes

The mechanism of insulin signaling on browning of white preadipocytes remains unclear. Human and mouse primary subcutaneous white preadipocytes (hsASCs and WT lean and obese msASCs, respectively) were induced to transdifferentiate into beige adipocytes under conditions of intact or blocked insulin s...

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Main Authors: Jie Pan, Suchart Kothan, Aye Thidar Moe Moe, Kun Huang
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Adipocyte
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/21623945.2022.2062852
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author Jie Pan
Suchart Kothan
Aye Thidar Moe Moe
Kun Huang
author_facet Jie Pan
Suchart Kothan
Aye Thidar Moe Moe
Kun Huang
author_sort Jie Pan
collection DOAJ
description The mechanism of insulin signaling on browning of white preadipocytes remains unclear. Human and mouse primary subcutaneous white preadipocytes (hsASCs and WT lean and obese msASCs, respectively) were induced to transdifferentiate into beige adipocytes under conditions of intact or blocked insulin signaling, respectively. Level of phosphoinositide-3-kinase (PI3K) after induction of beige adipocytes under conditions of normal insulin signaling, phosphorylated protein kinase B (pAKT), peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), zinc-fifinger transcriptional factor PRD1-BF1-RIZ1 homologous domain-containing protein 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein beta (C/EBPβ) were significantly increased. Conversely, when insulin signaling is incompletely inhibited, the expression of the thermogenic and adipogenic factors is significantly reduced, with obvious impairment of adipogenesis. However, phosphorylation level of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) and expression level of sirtuin type 1 (SIRT1) had increased. These white preadipocytes from different donors showed similar dynamic change in morphology and molecular levels during the browning. The present data indicate that insulin signaling plays a important role in regulation of browning of hsASCs and msASCs through PI3K-AKT-UCP1 signaling pathway. The insulin-AMPK-SIRT1 pathway was also involved in the adipocytes browning, while its effect is limited.
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spelling doaj.art-ceaa352f186a49bda4c1c6c1014131c32022-12-22T02:51:42ZengTaylor & Francis GroupAdipocyte2162-39452162-397X2022-12-0111121322610.1080/21623945.2022.2062852Dysfunction of insulin-AKT-UCP1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown-like adipocytesJie Pan0Suchart Kothan1Aye Thidar Moe Moe2Kun Huang3Shandong Provincial Key Laboratory of Animal Resistant Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong Province, ChinaCenter of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandCenter of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandShandong Provincial Key Laboratory of Animal Resistant Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong Province, ChinaThe mechanism of insulin signaling on browning of white preadipocytes remains unclear. Human and mouse primary subcutaneous white preadipocytes (hsASCs and WT lean and obese msASCs, respectively) were induced to transdifferentiate into beige adipocytes under conditions of intact or blocked insulin signaling, respectively. Level of phosphoinositide-3-kinase (PI3K) after induction of beige adipocytes under conditions of normal insulin signaling, phosphorylated protein kinase B (pAKT), peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), zinc-fifinger transcriptional factor PRD1-BF1-RIZ1 homologous domain-containing protein 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein beta (C/EBPβ) were significantly increased. Conversely, when insulin signaling is incompletely inhibited, the expression of the thermogenic and adipogenic factors is significantly reduced, with obvious impairment of adipogenesis. However, phosphorylation level of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) and expression level of sirtuin type 1 (SIRT1) had increased. These white preadipocytes from different donors showed similar dynamic change in morphology and molecular levels during the browning. The present data indicate that insulin signaling plays a important role in regulation of browning of hsASCs and msASCs through PI3K-AKT-UCP1 signaling pathway. The insulin-AMPK-SIRT1 pathway was also involved in the adipocytes browning, while its effect is limited.https://www.tandfonline.com/doi/10.1080/21623945.2022.2062852Insulin signallingAKTUCP1white preadipocytesbrowning
spellingShingle Jie Pan
Suchart Kothan
Aye Thidar Moe Moe
Kun Huang
Dysfunction of insulin-AKT-UCP1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown-like adipocytes
Adipocyte
Insulin signalling
AKT
UCP1
white preadipocytes
browning
title Dysfunction of insulin-AKT-UCP1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown-like adipocytes
title_full Dysfunction of insulin-AKT-UCP1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown-like adipocytes
title_fullStr Dysfunction of insulin-AKT-UCP1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown-like adipocytes
title_full_unstemmed Dysfunction of insulin-AKT-UCP1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown-like adipocytes
title_short Dysfunction of insulin-AKT-UCP1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown-like adipocytes
title_sort dysfunction of insulin akt ucp1 signalling inhibits transdifferentiation of human and mouse white preadipocytes into brown like adipocytes
topic Insulin signalling
AKT
UCP1
white preadipocytes
browning
url https://www.tandfonline.com/doi/10.1080/21623945.2022.2062852
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