AP2-NR4A3 transgenic mice display reduced serum epinephrine because of increased catecholamine catabolism in adipose tissue

R. Grace Walton, Xiaolin Zhu, Ling Tian, Elizabeth B. Heywood, Jian Liu, Helliner S. Hill, Jiarong Liu, Dennis Bruemmer, Qinglin Yang, Yuchang Fu, W. Timothy Garvey

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The NR4A orphan nuclear receptors function as early response genes to numerous stimuli. Our laboratory has previously demonstrated that overexpression of NR4A3 (NOR-1, MINOR) in 3T3-L1 adipocytes enhances insulinstimulated glucose uptake. To assess the in vivo effect of NR4A3 on adipocytes, we generated transgenic mice with NR4A3 overexpression driven by the adipocyte fatty acid-binding protein (AP2) promoter (AP2-NR4A3 mice). We hypothesized that AP2-NR4A3 mice would display enhanced glucose tolerance and insulin sensitivity. However, AP2-NR4A3 mice exhibit metabolic impairment, including increased fasting glucose and insulin, impaired glucose tolerance, insulin resistance, decreased serum free fatty acids, and increased low-density lipoprotein-cholesterol. AP2-NR4A3 mice also display a significant reduction in serum epinephrine due to increased expression of catecholamine-catabolizing enzymes in adipose tissue, including monoamine oxidase-A. Furthermore, enhanced expression of monoamine oxidase-A is due to direct transcriptional activation by NR4A3. Finally, AP2-NR4A3 mice display cardiac and behavioral alterations consistent with chronically low circulating epinephrine levels. In conclusion, overexpression of NR4A3 in adipocytes produces a complex phenotype characterized by impaired glucose metabolism and low serum catecholamines due to enhanced degradation by adipose tissue.

Original languageEnglish
Pages (from-to)E69-E81
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume311
Issue number1
DOIs
StatePublished - Jul 1 2016

Bibliographical note

Publisher Copyright:
© 2016 the American Physiological Society.

Keywords

  • Lipolysis
  • Monoamine oxidase
  • Nuclear receptor 4A3
  • Nuclear receptor 4A3 transgenic mice
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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