title: Hematopoietic cyclooxygenase-2 deficiency increases adipose tissue inflammation and adiposity in obesity.
abstract: OBJECTIVE
  Adipose tissue (AT) macrophages mediate AT inflammation in obesity, and cyclooxygenase-2 (COX-2) is a major inflammatory gene. It was hypothesized that deletion of hematopoietic COX-2 will inhibit AT inflammation in obesity.
  
  
  METHODS
  Lethally irradiated wild-type (WT) mice were injected with bone marrow (BM) cells collected from WT or COX-2 knock-out (COX-2-/-) donor mice and fed a high-fat diet for 16 weeks.
  
  
  RESULTS
  The mice that received BM cells from COX-2-/- mice (BM-COX-2-/-) gained increased body weight, fat mass, and visceral AT (VAT) mass. These mice exhibited reduced inflammatory markers in the VAT stromal vascular cells (SVC). However, the inflammatory markers were increased in adipocyte fraction and/or whole VAT. The activation of ERK1/2 MAPK, a pro-inflammatory signaling pathway, was increased in BM-COX-2-/- mice. The molecular markers of adipogenesis were increased in the VAT or adipocyte fraction. Wnt signaling markers which inhibit adipogenesis, including Wnt3A and DVL3, were reduced, and Wnt5a/b which promotes inflammation was increased in the VAT and/or adipocytes. Finally, an increase in hepatic triglyceride levels in BM-COX-2-/- mice was noted.
  
  
  CONCLUSIONS
  The data suggest that COX-2 deletion in hematopoietic cells reduces SVC inflammation but increases VAT inflammation and promotes adiposity likely via altered Wnt signaling.
authors: Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA.|Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA.
authors: Nikhil
authors: N
authors: Adi
authors: Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA.|Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA.
authors: Curtis
authors: C
authors: Perriotte-Olson
authors: Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA.|Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA.
authors: Cyrus V
authors: CV
authors: Desouza
authors: Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA.|Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA.
authors: Ramesh
authors: R
authors: Ramalingam
authors: Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, Nebraska, USA.|Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA.|Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors: Viswanathan
authors: V
authors: Saraswathi
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply*; D050154:Adiposity; D000818:Animals; D051546:Cyclooxygenase 2 / Q000172:deficiency*; D059305:Diet, High-Fat; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity
chemical_list: C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2