Journal
CELLS
Volume 11, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/cells11111819
Keywords
COX-2; PGE2; white adipogenesis; adipocyte hypertrophy; obesity; PPAR gamma
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [DK110439, DK132643]
- National Institute of General Medical Sciences [GM121176]
- American Heart Association [15GRNT24940018]
- American Diabetes Association [1-17-IBS-261]
- National Heart Lung and Blood Institute [HL148337]
- CoBRE pilot award [P30GM103400]
- Department of Health and Human Services Secretaries of National institution of Health [UL1TR001449]
- National Cancer Institute [CA118100]
- University of New Mexico School of Medicine
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The lack of COX-2 in adipocytes promotes white adipose tissue development and increases the size and number of adipocytes, leading to obesity and insulin resistance. Treatment with PGE2 can reverse the increased size and number of adipocytes caused by COX-2 knockout.
Cyclooxygenase-2 (COX-2) plays a critical role in regulating innate immunity and metabolism by producing prostaglandins (PGs) and other lipid mediators. However, the implication of adipose COX-2 in obesity remains largely unknown. Using adipocyte-specific COX-2 knockout (KO) mice, we showed that depleting COX-2 in adipocytes promoted white adipose tissue development accompanied with increased size and number of adipocytes and predisposed diet-induced adiposity, obesity, and insulin resistance. The increased size and number of adipocytes by COX-2 KO were reversed by the treatment of prostaglandin E2 (PGE2) but not PGI2 and PGD2 during adipocyte differentiation. PGE2 suppresses PPAR gamma expression through the PKA pathway at the early phase of adipogenesis, and treatment of PGE2 or PKA activator isoproterenol diminished the increased lipid droplets in size and number in COX-2 KO primary adipocytes. Administration of PGE2 attenuated increased fat mass and fat percentage in COX-2 deficient mice. Taken together, our study demonstrated the suppressing effect of adipocyte COX-2 on adipogenesis and reveals that COX-2 restrains adipose tissue expansion via the PGE2-mediated paracrine mechanism and prevents the development of obesity and related metabolic disorders.
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