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 journalArticlepeer-review

155 Scopus citations


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)
Pages (from-to)C386-C394
JournalAmerican Journal of Physiology - Cell Physiology
Issue number2 45-2
StatePublished - 1999


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

ASJC Scopus subject areas

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


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