COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity
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 dep...
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MDPI AG
2022-06-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/11/1819 |
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| author | Chunqing Wang Xing Zhang Liping Luo Yan Luo Dandan Wu Dianna Spilca Que Le Xin Yang Katelyn Alvarez William Curtis Hines Xuexian O. Yang Meilian Liu |
| author_facet | Chunqing Wang Xing Zhang Liping Luo Yan Luo Dandan Wu Dianna Spilca Que Le Xin Yang Katelyn Alvarez William Curtis Hines Xuexian O. Yang Meilian Liu |
| author_sort | Chunqing Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T01:25:19Z |
| format | Article |
| id | doaj.art-e8ee6e7b68fe4350bd4c8741f37ce71b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:25:19Z |
| publishDate | 2022-06-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-e8ee6e7b68fe4350bd4c8741f37ce71b2023-11-23T13:53:18ZengMDPI AGCells2073-44092022-06-011111181910.3390/cells11111819COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced ObesityChunqing Wang0Xing Zhang1Liping Luo2Yan Luo3Dandan Wu4Dianna Spilca5Que Le6Xin Yang7Katelyn Alvarez8William Curtis Hines9Xuexian O. Yang10Meilian Liu11Department of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USACyclooxygenase-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.https://www.mdpi.com/2073-4409/11/11/1819COX-2PGE2white adipogenesisadipocyte hypertrophyobesityPPARγ |
| spellingShingle | Chunqing Wang Xing Zhang Liping Luo Yan Luo Dandan Wu Dianna Spilca Que Le Xin Yang Katelyn Alvarez William Curtis Hines Xuexian O. Yang Meilian Liu COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity Cells COX-2 PGE2 white adipogenesis adipocyte hypertrophy obesity PPARγ |
| title | COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity |
| title_full | COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity |
| title_fullStr | COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity |
| title_full_unstemmed | COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity |
| title_short | COX-2 Deficiency Promotes White Adipogenesis via PGE2-Mediated Paracrine Mechanism and Exacerbates Diet-Induced Obesity |
| title_sort | cox 2 deficiency promotes white adipogenesis via pge2 mediated paracrine mechanism and exacerbates diet induced obesity |
| topic | COX-2 PGE2 white adipogenesis adipocyte hypertrophy obesity PPARγ |
| url | https://www.mdpi.com/2073-4409/11/11/1819 |
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