Phenotypic abnormalities in macrophages from leptin-deficient, obese mice

Fung Yee Lee Janet, L. I. Yunbo, Eun K. Yang, Shi Q I Yang, Hui Lin Zhi, Michael A. Trush, Andrew J. Dannenberg, Anna Mae Diehl

Research output: Contribution to journalArticle

Abstract

Obesity is a complex syndrome that involves defective signaling by a number of different factors that regulate appetite and energy homeostasis. Treatment with exogenous leptin reverses hyperphagia and obesity in ob/ob mice, which have a mutation that causes leptin deficiency, proving the importance of this factor and its receptors in the obesity syndrome. Cells with leptin receptors have been identified outside of the appetite regulatory centers in the brain. Thus leptin has peripheral targets. Because macrophages express signaling-competent leptin receptors, these cells may be altered during chronic leptin deficiency. Consistent with this concept, the present study identifies several phenotypic abnormalities in macrophages from ob/ob mice, including decreased steady-state levels of uncoupling protein-2 mRNA, increased mitochondrial production of superoxide and hydrogen peroxide, constitutive activation of CCAAT enhancer binding protein (C/EBP)-β, an oxidant-sensitive transcription factor, increased expression of interleukin- 6 and cyclooxygenase (COX)-2, two C/EBP-β target genes, and increased COX- 2-dependent production of PGE2. Given the importance of macrophages in the general regulation of inflammation and immunity, these alterations in macrophage function may contribute to obesity-related pathophysiology.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number2 45-2
StatePublished - 1999

Fingerprint

Obese Mice
Macrophages
Leptin
Obesity
CCAAT-Enhancer-Binding Proteins
Leptin Receptors
Appetite
Cyclooxygenase 2
Hyperphagia
Dinoprostone
Oxidants
Superoxides
Hydrogen Peroxide
Immunity
Interleukin-6
Brain
Homeostasis
Transcription Factors
Genes
Chemical activation

Keywords

  • Cyclooxygenase-2
  • Cytokines
  • Obesity
  • Superoxide
  • Uncoupling proteins

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Lee Janet, F. Y., Yunbo, L. I., Yang, E. K., Yang, S. Q. I., Lin Zhi, H., Trush, M. A., ... Diehl, A. M. (1999). Phenotypic abnormalities in macrophages from leptin-deficient, obese mice. American Journal of Physiology - Cell Physiology, 276(2 45-2).

Phenotypic abnormalities in macrophages from leptin-deficient, obese mice. / Lee Janet, Fung Yee; Yunbo, L. I.; Yang, Eun K.; Yang, Shi Q I; Lin Zhi, Hui; Trush, Michael A.; Dannenberg, Andrew J.; Diehl, Anna Mae.

In: American Journal of Physiology - Cell Physiology, Vol. 276, No. 2 45-2, 1999.

Research output: Contribution to journalArticle

Lee Janet, FY, Yunbo, LI, Yang, EK, Yang, SQI, Lin Zhi, H, Trush, MA, Dannenberg, AJ & Diehl, AM 1999, 'Phenotypic abnormalities in macrophages from leptin-deficient, obese mice', American Journal of Physiology - Cell Physiology, vol. 276, no. 2 45-2.
Lee Janet FY, Yunbo LI, Yang EK, Yang SQI, Lin Zhi H, Trush MA et al. Phenotypic abnormalities in macrophages from leptin-deficient, obese mice. American Journal of Physiology - Cell Physiology. 1999;276(2 45-2).
Lee Janet, Fung Yee ; Yunbo, L. I. ; Yang, Eun K. ; Yang, Shi Q I ; Lin Zhi, Hui ; Trush, Michael A. ; Dannenberg, Andrew J. ; Diehl, Anna Mae. / Phenotypic abnormalities in macrophages from leptin-deficient, obese mice. In: American Journal of Physiology - Cell Physiology. 1999 ; Vol. 276, No. 2 45-2.
@article{76810cbfd5484df394759a71a255a202,
title = "Phenotypic abnormalities in macrophages from leptin-deficient, obese mice",
abstract = "Obesity is a complex syndrome that involves defective signaling by a number of different factors that regulate appetite and energy homeostasis. Treatment with exogenous leptin reverses hyperphagia and obesity in ob/ob mice, which have a mutation that causes leptin deficiency, proving the importance of this factor and its receptors in the obesity syndrome. Cells with leptin receptors have been identified outside of the appetite regulatory centers in the brain. Thus leptin has peripheral targets. Because macrophages express signaling-competent leptin receptors, these cells may be altered during chronic leptin deficiency. Consistent with this concept, the present study identifies several phenotypic abnormalities in macrophages from ob/ob mice, including decreased steady-state levels of uncoupling protein-2 mRNA, increased mitochondrial production of superoxide and hydrogen peroxide, constitutive activation of CCAAT enhancer binding protein (C/EBP)-β, an oxidant-sensitive transcription factor, increased expression of interleukin- 6 and cyclooxygenase (COX)-2, two C/EBP-β target genes, and increased COX- 2-dependent production of PGE2. Given the importance of macrophages in the general regulation of inflammation and immunity, these alterations in macrophage function may contribute to obesity-related pathophysiology.",
keywords = "Cyclooxygenase-2, Cytokines, Obesity, Superoxide, Uncoupling proteins",
author = "{Lee Janet}, {Fung Yee} and Yunbo, {L. I.} and Yang, {Eun K.} and Yang, {Shi Q I} and {Lin Zhi}, Hui and Trush, {Michael A.} and Dannenberg, {Andrew J.} and Diehl, {Anna Mae}",
year = "1999",
language = "English (US)",
volume = "276",
journal = "American Journal of Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "2 45-2",

}

TY - JOUR

T1 - Phenotypic abnormalities in macrophages from leptin-deficient, obese mice

AU - Lee Janet, Fung Yee

AU - Yunbo, L. I.

AU - Yang, Eun K.

AU - Yang, Shi Q I

AU - Lin Zhi, Hui

AU - Trush, Michael A.

AU - Dannenberg, Andrew J.

AU - Diehl, Anna Mae

PY - 1999

Y1 - 1999

N2 - Obesity is a complex syndrome that involves defective signaling by a number of different factors that regulate appetite and energy homeostasis. Treatment with exogenous leptin reverses hyperphagia and obesity in ob/ob mice, which have a mutation that causes leptin deficiency, proving the importance of this factor and its receptors in the obesity syndrome. Cells with leptin receptors have been identified outside of the appetite regulatory centers in the brain. Thus leptin has peripheral targets. Because macrophages express signaling-competent leptin receptors, these cells may be altered during chronic leptin deficiency. Consistent with this concept, the present study identifies several phenotypic abnormalities in macrophages from ob/ob mice, including decreased steady-state levels of uncoupling protein-2 mRNA, increased mitochondrial production of superoxide and hydrogen peroxide, constitutive activation of CCAAT enhancer binding protein (C/EBP)-β, an oxidant-sensitive transcription factor, increased expression of interleukin- 6 and cyclooxygenase (COX)-2, two C/EBP-β target genes, and increased COX- 2-dependent production of PGE2. Given the importance of macrophages in the general regulation of inflammation and immunity, these alterations in macrophage function may contribute to obesity-related pathophysiology.

AB - Obesity is a complex syndrome that involves defective signaling by a number of different factors that regulate appetite and energy homeostasis. Treatment with exogenous leptin reverses hyperphagia and obesity in ob/ob mice, which have a mutation that causes leptin deficiency, proving the importance of this factor and its receptors in the obesity syndrome. Cells with leptin receptors have been identified outside of the appetite regulatory centers in the brain. Thus leptin has peripheral targets. Because macrophages express signaling-competent leptin receptors, these cells may be altered during chronic leptin deficiency. Consistent with this concept, the present study identifies several phenotypic abnormalities in macrophages from ob/ob mice, including decreased steady-state levels of uncoupling protein-2 mRNA, increased mitochondrial production of superoxide and hydrogen peroxide, constitutive activation of CCAAT enhancer binding protein (C/EBP)-β, an oxidant-sensitive transcription factor, increased expression of interleukin- 6 and cyclooxygenase (COX)-2, two C/EBP-β target genes, and increased COX- 2-dependent production of PGE2. Given the importance of macrophages in the general regulation of inflammation and immunity, these alterations in macrophage function may contribute to obesity-related pathophysiology.

KW - Cyclooxygenase-2

KW - Cytokines

KW - Obesity

KW - Superoxide

KW - Uncoupling proteins

UR - http://www.scopus.com/inward/record.url?scp=0009912839&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0009912839&partnerID=8YFLogxK

M3 - Article

C2 - 9950766

AN - SCOPUS:0009912839

VL - 276

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6135

IS - 2 45-2

ER -