Impact of hematopoietic cyclooxygenase-1 deficiency on obesity-linked adipose tissue inflammation and metabolic disorders in mice

Saraswathi Viswanathan, Christopher J. Ramnanan, Anson W. Wilks, Cyrus V Desouza, Amy A. Eller, Ganesan Murali, Ramesh Ramalingam, Ginger L. Milne, Katie C. Coate, Dale S. Edgerton

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Objective Adipose tissue (AT)-specific inflammation is considered to mediate the pathological consequences of obesity and macrophages are known to activate inflammatory pathways in obese AT. Because cyclooxygenases play a central role in regulating the inflammatory processes, we sought to determine the role of hematopoietic cyclooxygenase-1 (COX-1) in modulating AT inflammation in obesity. Materials/Methods Bone marrow transplantation was performed to delete COX-1 in hematopoietic cells. Briefly, female wild type (wt) mice were lethally irradiated and injected with bone marrow (BM) cells collected from wild type (COX-1 +/+) or COX-1 knock-out (COX-1 -/-) donor mice. The mice were fed a high fat diet for 16 weeks. Results The mice that received COX-1 -/- bone marrow (BM-COX-1 -/-) exhibited a significant increase in fasting glucose, total cholesterol and triglycerides in the circulation compared to control (BM-COX-1 +/+) mice. Markers of AT-inflammation were increased and were associated with increased leptin and decreased adiponectin in plasma. Hepatic inflammation was reduced with a concomitant reduction in TXB2 levels. The hepatic mRNA expression of genes involved in lipogenesis and lipid transport was increased while expression of genes involved in regulating hepatic glucose output was reduced in BM-COX-1 -/- mice. Finally, renal inflammation and markers of renal glucose release were increased in BM-COX-1 -/- mice. Conclusion Hematopoietic COX-1 deletion results in impairments in metabolic homeostasis which may be partly due to increased AT inflammation and dysregulated adipokine profile. An increase in renal glucose release and hepatic lipogenesis/lipid transport may also play a role, at least in part, in mediating hyperglycemia and dyslipidemia, respectively.

Original languageEnglish (US)
Pages (from-to)1673-1685
Number of pages13
JournalMetabolism: Clinical and Experimental
Volume62
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • Dyslipidemia
  • Eicosanoids
  • Hyperglycemia
  • Obesity

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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