Hematopoietic cyclooxygenase‐2 deficiency increases adipose tissue inflammation and adiposity in obesity

• Published in: Obesity (Silver Spring, Md.) Md.), 2015-10, Vol.23 (10), p.2037-2045
• Main Authors: Adi, Nikhil, Perriotte‐Olson, Curtis, V. Desouza, Cyrus, Ramalingam, Ramesh, Saraswathi, Viswanathan
• Format: Article
• Language: English
• Subjects: Adipose Tissue - blood supply; Adiposity; Animals; Body fat; Bone marrow; Cyclooxygenase 2 - deficiency; Diet, High-Fat; Inflammation - physiopathology; Insulin resistance; Laboratories; Metabolites; Mice; Mice, Inbred C57BL; Obesity; Transplants & implants
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1002/oby.21184

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.