Peroxisome proliferator-activated receptor γ and its role in adipocyte homeostasis and thiazolidinedione-mediated insulin sensitization

Qiong A. Wang, Fang Zhang, Lei Jiang, Risheng Ye, Yu An, Mengle Shao, Caroline Tao, Rana K Gupta, Philipp E Scherer

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Adipose tissue is a dynamic organ that makes critical contributions to whole-body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, peroxisome proliferator-activated receptor γ (PPARγ) is still widely viewed as the master regulator of adipogenesis and critical for maintaining mature adipocyte function. Using an inducible, adipocyte-specific knockout system, we explored the role of PPARγ in mature adipocytes in vivo. Short-term PPARγ deficiency in adipocytes reduces whole-body insulin sensitivity, but adipocytes are viable both in vitro and in vivo. However, after exposure to a high-fat diet, even short-term PPARγ deficiency leads to rapid adipocyte death. When mature adipocytes are depleted of both PPARγ and CCAAT-enhancer-binding protein α (C/EBPα), they are rapidly depleted of lipids and undergo adipocyte death, both in vitro and in vivo. Surprisingly, although thiazolidinediones (TZDs; PPARγ agonists) are thought to act mainly on PPARγ, PPARγ in adipocytes is not required for the whole-body insulinsensitizing effect of TZDs. This offers new mechanistic aspects of PPARγ/TZD action and its effect on whole-body metabolic homeostasis.

Original languageEnglish (US)
Article numbere00677
JournalMolecular and Cellular Biology
Volume38
Issue number10
DOIs
StatePublished - May 1 2018

Fingerprint

Peroxisome Proliferator-Activated Receptors
Adipocytes
Homeostasis
Insulin
CCAAT-Enhancer-Binding Proteins
2,4-thiazolidinedione
Thiazolidinediones
Adipogenesis
High Fat Diet
Insulin Resistance
Adipose Tissue
Fats
Lipids

Keywords

  • Adipocyte
  • Adipose tissue
  • C/EBPα
  • Inducible knockout
  • Insulin sensitization
  • Mouse model
  • Obesity
  • PPARγ
  • Thiazolidinedione

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Peroxisome proliferator-activated receptor γ and its role in adipocyte homeostasis and thiazolidinedione-mediated insulin sensitization. / Wang, Qiong A.; Zhang, Fang; Jiang, Lei; Ye, Risheng; An, Yu; Shao, Mengle; Tao, Caroline; Gupta, Rana K; Scherer, Philipp E.

In: Molecular and Cellular Biology, Vol. 38, No. 10, e00677, 01.05.2018.

Research output: Contribution to journalArticle

@article{20bc90ad3c4948b6911c770dbb4b7a80,
title = "Peroxisome proliferator-activated receptor γ and its role in adipocyte homeostasis and thiazolidinedione-mediated insulin sensitization",
abstract = "Adipose tissue is a dynamic organ that makes critical contributions to whole-body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, peroxisome proliferator-activated receptor γ (PPARγ) is still widely viewed as the master regulator of adipogenesis and critical for maintaining mature adipocyte function. Using an inducible, adipocyte-specific knockout system, we explored the role of PPARγ in mature adipocytes in vivo. Short-term PPARγ deficiency in adipocytes reduces whole-body insulin sensitivity, but adipocytes are viable both in vitro and in vivo. However, after exposure to a high-fat diet, even short-term PPARγ deficiency leads to rapid adipocyte death. When mature adipocytes are depleted of both PPARγ and CCAAT-enhancer-binding protein α (C/EBPα), they are rapidly depleted of lipids and undergo adipocyte death, both in vitro and in vivo. Surprisingly, although thiazolidinediones (TZDs; PPARγ agonists) are thought to act mainly on PPARγ, PPARγ in adipocytes is not required for the whole-body insulinsensitizing effect of TZDs. This offers new mechanistic aspects of PPARγ/TZD action and its effect on whole-body metabolic homeostasis.",
keywords = "Adipocyte, Adipose tissue, C/EBPα, Inducible knockout, Insulin sensitization, Mouse model, Obesity, PPARγ, Thiazolidinedione",
author = "Wang, {Qiong A.} and Fang Zhang and Lei Jiang and Risheng Ye and Yu An and Mengle Shao and Caroline Tao and Gupta, {Rana K} and Scherer, {Philipp E}",
year = "2018",
month = "5",
day = "1",
doi = "10.1128/MCB.00677-17",
language = "English (US)",
volume = "38",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "10",

}

TY - JOUR

T1 - Peroxisome proliferator-activated receptor γ and its role in adipocyte homeostasis and thiazolidinedione-mediated insulin sensitization

AU - Wang, Qiong A.

AU - Zhang, Fang

AU - Jiang, Lei

AU - Ye, Risheng

AU - An, Yu

AU - Shao, Mengle

AU - Tao, Caroline

AU - Gupta, Rana K

AU - Scherer, Philipp E

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Adipose tissue is a dynamic organ that makes critical contributions to whole-body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, peroxisome proliferator-activated receptor γ (PPARγ) is still widely viewed as the master regulator of adipogenesis and critical for maintaining mature adipocyte function. Using an inducible, adipocyte-specific knockout system, we explored the role of PPARγ in mature adipocytes in vivo. Short-term PPARγ deficiency in adipocytes reduces whole-body insulin sensitivity, but adipocytes are viable both in vitro and in vivo. However, after exposure to a high-fat diet, even short-term PPARγ deficiency leads to rapid adipocyte death. When mature adipocytes are depleted of both PPARγ and CCAAT-enhancer-binding protein α (C/EBPα), they are rapidly depleted of lipids and undergo adipocyte death, both in vitro and in vivo. Surprisingly, although thiazolidinediones (TZDs; PPARγ agonists) are thought to act mainly on PPARγ, PPARγ in adipocytes is not required for the whole-body insulinsensitizing effect of TZDs. This offers new mechanistic aspects of PPARγ/TZD action and its effect on whole-body metabolic homeostasis.

AB - Adipose tissue is a dynamic organ that makes critical contributions to whole-body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, peroxisome proliferator-activated receptor γ (PPARγ) is still widely viewed as the master regulator of adipogenesis and critical for maintaining mature adipocyte function. Using an inducible, adipocyte-specific knockout system, we explored the role of PPARγ in mature adipocytes in vivo. Short-term PPARγ deficiency in adipocytes reduces whole-body insulin sensitivity, but adipocytes are viable both in vitro and in vivo. However, after exposure to a high-fat diet, even short-term PPARγ deficiency leads to rapid adipocyte death. When mature adipocytes are depleted of both PPARγ and CCAAT-enhancer-binding protein α (C/EBPα), they are rapidly depleted of lipids and undergo adipocyte death, both in vitro and in vivo. Surprisingly, although thiazolidinediones (TZDs; PPARγ agonists) are thought to act mainly on PPARγ, PPARγ in adipocytes is not required for the whole-body insulinsensitizing effect of TZDs. This offers new mechanistic aspects of PPARγ/TZD action and its effect on whole-body metabolic homeostasis.

KW - Adipocyte

KW - Adipose tissue

KW - C/EBPα

KW - Inducible knockout

KW - Insulin sensitization

KW - Mouse model

KW - Obesity

KW - PPARγ

KW - Thiazolidinedione

UR - http://www.scopus.com/inward/record.url?scp=85046543476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046543476&partnerID=8YFLogxK

U2 - 10.1128/MCB.00677-17

DO - 10.1128/MCB.00677-17

M3 - Article

VL - 38

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 10

M1 - e00677

ER -