COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity
Year: 2022
Type: article
Abstract: 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 PPARγ 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.
Source: Cells
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,303
Funders: American Diabetes Association, American Heart Association, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: Collaboration to enhance Naloxone Dispensing in Rural and Underserved Areas (CONsiDER), G1361504940, G1376570166, G1602140153, G1626570795, G1644169990, G1722050301, G1798982246, G1849608474, The Role of Adiponectin in Regulating Group 2 Innate Lymphoid Cells and Browning in Fat, G2126012127, G2211376075, G2253994533, G2314402734, G2364574140, G2578231927, G2593167697, G2682165699, G2716354579, G289889527, G2961653715, G3068102844, G3194648055, G3295474147, G3579987266, G3642291323, The role of mTORC1 and Autophagy in the Recruitment and Activation of Beige Adipocytes, The Cytokine Suppressor CIS in Giant Cell Pneumonitis, G4094384561, Integrative Program in CNS Pathophysiology Research, G4157997047, G4498423455, G4527312025, G4538094658, G4876802509, G5100821750, G5607939598, Institute for Integration of Medicine & Science: A Partnership to Improve Health, G5790645282, G5858212201, G5880394204, G701266403, G7047137344, University of New Mexico Cancer Center Support, G7221008527, G77486010, G7934728508, G8527536484, G8584148344, G8656573895, Autophagy, Inflammation and Metabolism (AIM) in Disease Center - Phase 2., Transcriptional Control of High-thermogenic Adipocyte Development
OpenAlex ID: W4281661867