Macrophage elastase suppresses white adipose tissue expansion with cigarette smoking

Takao Tsuji, Neil J. Kelly, Saeko Takahashi, Adriana S. Leme, A. McGarry Houghton, Steven D. Shapiro

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced emphysema, yet its role in other smoking related pathologies remains unclear. The weight suppressing effects of smoking are a major hindrance to cessation efforts, and MMP12 is known to suppress the vascularization on which adipose tissue growth depends by catalyzing the formation of antiangiogenic peptides endostatin and angiostatin. The goal of this study was to determine the role of MMP12 in adipose tissue growth and smoking-related suppression of weight gain. Whole body weights and white adipose depots from wild-type and Mmp12-deficient mice were collected during early postnatal development and after chronic CS exposure. Adipose tissue specimens were analyzed for angiogenic and adipocytic markers and for content of the antiangiogenic peptides endostatin and angiostatin. Cultured 3T3-L1 adipocytes were treated with adipose tissue homogenate to examine its effects on vascular endothelial growth factor (VEGF) expression and secretion. MMP12 content and activity were increased in the adipose tissue of wild-type mice at 2 weeks of age, leading to elevated endostatin production, inhibition of VEGF secretion, and decreased adipose tissue vascularity. By 8 weeks of age, adipose MMP12 levels subsided, and the protein was no longer detectable. However, chronic CS exposure led to macrophage accumulation and restored adipose MMP12 activity, thereby suppressing adipose tissue mass and vascularity. Our results reveal a novel systemic role for MMP12 in postnatal adipose tissue expansion and smoking-associated weight loss by suppressing vascularity within the white adipose tissue depots.

Original languageEnglish
Pages (from-to)822-829
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume51
Issue number6
DOIs
Publication statusPublished - 2014 Dec 1

Fingerprint

Tissue Expansion
White Adipose Tissue
Macrophages
Pancreatic Elastase
Tobacco Products
Adipose Tissue
Smoking
Tissue
Endostatins
Angiostatins
Smoke
Vascular Endothelial Growth Factor A
Peptides
Emphysema
Growth
Adipocytes
Pathology
Weight Gain
Weight Loss
Body Weight

Keywords

  • Angiogenesis
  • Obesity
  • Proteases

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Macrophage elastase suppresses white adipose tissue expansion with cigarette smoking. / Tsuji, Takao; Kelly, Neil J.; Takahashi, Saeko; Leme, Adriana S.; Houghton, A. McGarry; Shapiro, Steven D.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 51, No. 6, 01.12.2014, p. 822-829.

Research output: Contribution to journalArticle

Tsuji, Takao ; Kelly, Neil J. ; Takahashi, Saeko ; Leme, Adriana S. ; Houghton, A. McGarry ; Shapiro, Steven D. / Macrophage elastase suppresses white adipose tissue expansion with cigarette smoking. In: American Journal of Respiratory Cell and Molecular Biology. 2014 ; Vol. 51, No. 6. pp. 822-829.
@article{1d7e7834431a4f5f947a5f572176e3d1,
title = "Macrophage elastase suppresses white adipose tissue expansion with cigarette smoking",
abstract = "Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced emphysema, yet its role in other smoking related pathologies remains unclear. The weight suppressing effects of smoking are a major hindrance to cessation efforts, and MMP12 is known to suppress the vascularization on which adipose tissue growth depends by catalyzing the formation of antiangiogenic peptides endostatin and angiostatin. The goal of this study was to determine the role of MMP12 in adipose tissue growth and smoking-related suppression of weight gain. Whole body weights and white adipose depots from wild-type and Mmp12-deficient mice were collected during early postnatal development and after chronic CS exposure. Adipose tissue specimens were analyzed for angiogenic and adipocytic markers and for content of the antiangiogenic peptides endostatin and angiostatin. Cultured 3T3-L1 adipocytes were treated with adipose tissue homogenate to examine its effects on vascular endothelial growth factor (VEGF) expression and secretion. MMP12 content and activity were increased in the adipose tissue of wild-type mice at 2 weeks of age, leading to elevated endostatin production, inhibition of VEGF secretion, and decreased adipose tissue vascularity. By 8 weeks of age, adipose MMP12 levels subsided, and the protein was no longer detectable. However, chronic CS exposure led to macrophage accumulation and restored adipose MMP12 activity, thereby suppressing adipose tissue mass and vascularity. Our results reveal a novel systemic role for MMP12 in postnatal adipose tissue expansion and smoking-associated weight loss by suppressing vascularity within the white adipose tissue depots.",
keywords = "Angiogenesis, Obesity, Proteases",
author = "Takao Tsuji and Kelly, {Neil J.} and Saeko Takahashi and Leme, {Adriana S.} and Houghton, {A. McGarry} and Shapiro, {Steven D.}",
year = "2014",
month = "12",
day = "1",
doi = "10.1165/rcmb.2014-0083OC",
language = "English",
volume = "51",
pages = "822--829",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "6",

}

TY - JOUR

T1 - Macrophage elastase suppresses white adipose tissue expansion with cigarette smoking

AU - Tsuji, Takao

AU - Kelly, Neil J.

AU - Takahashi, Saeko

AU - Leme, Adriana S.

AU - Houghton, A. McGarry

AU - Shapiro, Steven D.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced emphysema, yet its role in other smoking related pathologies remains unclear. The weight suppressing effects of smoking are a major hindrance to cessation efforts, and MMP12 is known to suppress the vascularization on which adipose tissue growth depends by catalyzing the formation of antiangiogenic peptides endostatin and angiostatin. The goal of this study was to determine the role of MMP12 in adipose tissue growth and smoking-related suppression of weight gain. Whole body weights and white adipose depots from wild-type and Mmp12-deficient mice were collected during early postnatal development and after chronic CS exposure. Adipose tissue specimens were analyzed for angiogenic and adipocytic markers and for content of the antiangiogenic peptides endostatin and angiostatin. Cultured 3T3-L1 adipocytes were treated with adipose tissue homogenate to examine its effects on vascular endothelial growth factor (VEGF) expression and secretion. MMP12 content and activity were increased in the adipose tissue of wild-type mice at 2 weeks of age, leading to elevated endostatin production, inhibition of VEGF secretion, and decreased adipose tissue vascularity. By 8 weeks of age, adipose MMP12 levels subsided, and the protein was no longer detectable. However, chronic CS exposure led to macrophage accumulation and restored adipose MMP12 activity, thereby suppressing adipose tissue mass and vascularity. Our results reveal a novel systemic role for MMP12 in postnatal adipose tissue expansion and smoking-associated weight loss by suppressing vascularity within the white adipose tissue depots.

AB - Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced emphysema, yet its role in other smoking related pathologies remains unclear. The weight suppressing effects of smoking are a major hindrance to cessation efforts, and MMP12 is known to suppress the vascularization on which adipose tissue growth depends by catalyzing the formation of antiangiogenic peptides endostatin and angiostatin. The goal of this study was to determine the role of MMP12 in adipose tissue growth and smoking-related suppression of weight gain. Whole body weights and white adipose depots from wild-type and Mmp12-deficient mice were collected during early postnatal development and after chronic CS exposure. Adipose tissue specimens were analyzed for angiogenic and adipocytic markers and for content of the antiangiogenic peptides endostatin and angiostatin. Cultured 3T3-L1 adipocytes were treated with adipose tissue homogenate to examine its effects on vascular endothelial growth factor (VEGF) expression and secretion. MMP12 content and activity were increased in the adipose tissue of wild-type mice at 2 weeks of age, leading to elevated endostatin production, inhibition of VEGF secretion, and decreased adipose tissue vascularity. By 8 weeks of age, adipose MMP12 levels subsided, and the protein was no longer detectable. However, chronic CS exposure led to macrophage accumulation and restored adipose MMP12 activity, thereby suppressing adipose tissue mass and vascularity. Our results reveal a novel systemic role for MMP12 in postnatal adipose tissue expansion and smoking-associated weight loss by suppressing vascularity within the white adipose tissue depots.

KW - Angiogenesis

KW - Obesity

KW - Proteases

UR - http://www.scopus.com/inward/record.url?scp=84918840073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84918840073&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2014-0083OC

DO - 10.1165/rcmb.2014-0083OC

M3 - Article

VL - 51

SP - 822

EP - 829

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 6

ER -