Melatonin Regulates Lipid Metabolism in Porcine Cumulus–Oocyte Complexes via the Melatonin Receptor 2
Previous studies suggest that the inclusion of melatonin (MTn) in in vitro maturation protocols improves the developmental competence of oocytes by scavenging reactive oxygen species (ROS). However, the molecular mechanisms integrating melatonin receptor (MT)-mediated lipid metabolism and redox sign...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/11/4/687 |
| _version_ | 1827621888735576064 |
|---|---|
| author | Jun-Xue Jin Jing-Tao Sun Chao-Qian Jiang Hong-Di Cui Ya Bian Sanghoon Lee Lianjin Zhang Byeong Chun Lee Zhong-Hua Liu |
| author_facet | Jun-Xue Jin Jing-Tao Sun Chao-Qian Jiang Hong-Di Cui Ya Bian Sanghoon Lee Lianjin Zhang Byeong Chun Lee Zhong-Hua Liu |
| author_sort | Jun-Xue Jin |
| collection | DOAJ |
| description | Previous studies suggest that the inclusion of melatonin (MTn) in in vitro maturation protocols improves the developmental competence of oocytes by scavenging reactive oxygen species (ROS). However, the molecular mechanisms integrating melatonin receptor (MT)-mediated lipid metabolism and redox signaling during in vitro cumulus–oocyte complex (COC) development still remain unclear. Here, we aimed to elucidate the potential role of MTn receptors in lipid metabolic adjustments during in vitro porcine COC development. We observed that MTn-mediated G<sub>s</sub>α–cAMP/PKA signaling facilitated lipolysis primarily through the MT2 receptor and subsequently increased fatty acid (FA) release by hydrolyzing intracellular triglycerides (TGs) in cumulus cells. Furthermore, <i>CD36</i> was a critical FA transporter that transported available FAs from cumulus cells to oocytes and promoted de novo TG synthesis in the latter. In addition, MTn regulated lipogenesis and intracellular lipolysis to maintain lipid homeostasis and limit ROS production, thereby supporting oocyte cytoplasmic maturation and the subsequent embryo development. Taken together, these findings provide insight into the possible mechanism integrating MT2-mediated lipid homeostasis and redox signaling, which limits ROS production during in vitro COC development. Therefore, understanding the dynamics of the interactions between lipid homeostasis and redox signaling driven by MT2 is necessary in order to predict drug targets and the effects of therapeutics used to improve female reproductive health. |
| first_indexed | 2024-03-09T11:13:34Z |
| format | Article |
| id | doaj.art-001016c743234fada8250f92bccd6383 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T11:13:34Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-001016c743234fada8250f92bccd63832023-12-01T00:35:05ZengMDPI AGAntioxidants2076-39212022-03-0111468710.3390/antiox11040687Melatonin Regulates Lipid Metabolism in Porcine Cumulus–Oocyte Complexes via the Melatonin Receptor 2Jun-Xue Jin0Jing-Tao Sun1Chao-Qian Jiang2Hong-Di Cui3Ya Bian4Sanghoon Lee5Lianjin Zhang6Byeong Chun Lee7Zhong-Hua Liu8Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, ChinaKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, ChinaKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, ChinaKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, ChinaKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, ChinaDepartment of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul 08826, KoreaDepartment of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 34141, KoreaDepartment of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul 08826, KoreaKey Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, ChinaPrevious studies suggest that the inclusion of melatonin (MTn) in in vitro maturation protocols improves the developmental competence of oocytes by scavenging reactive oxygen species (ROS). However, the molecular mechanisms integrating melatonin receptor (MT)-mediated lipid metabolism and redox signaling during in vitro cumulus–oocyte complex (COC) development still remain unclear. Here, we aimed to elucidate the potential role of MTn receptors in lipid metabolic adjustments during in vitro porcine COC development. We observed that MTn-mediated G<sub>s</sub>α–cAMP/PKA signaling facilitated lipolysis primarily through the MT2 receptor and subsequently increased fatty acid (FA) release by hydrolyzing intracellular triglycerides (TGs) in cumulus cells. Furthermore, <i>CD36</i> was a critical FA transporter that transported available FAs from cumulus cells to oocytes and promoted de novo TG synthesis in the latter. In addition, MTn regulated lipogenesis and intracellular lipolysis to maintain lipid homeostasis and limit ROS production, thereby supporting oocyte cytoplasmic maturation and the subsequent embryo development. Taken together, these findings provide insight into the possible mechanism integrating MT2-mediated lipid homeostasis and redox signaling, which limits ROS production during in vitro COC development. Therefore, understanding the dynamics of the interactions between lipid homeostasis and redox signaling driven by MT2 is necessary in order to predict drug targets and the effects of therapeutics used to improve female reproductive health.https://www.mdpi.com/2076-3921/11/4/687melatonin receptorlipid metabolismreactive oxygen speciescytoplasmic maturationcumulus–oocyte complexes |
| spellingShingle | Jun-Xue Jin Jing-Tao Sun Chao-Qian Jiang Hong-Di Cui Ya Bian Sanghoon Lee Lianjin Zhang Byeong Chun Lee Zhong-Hua Liu Melatonin Regulates Lipid Metabolism in Porcine Cumulus–Oocyte Complexes via the Melatonin Receptor 2 Antioxidants melatonin receptor lipid metabolism reactive oxygen species cytoplasmic maturation cumulus–oocyte complexes |
| title | Melatonin Regulates Lipid Metabolism in Porcine Cumulus–Oocyte Complexes via the Melatonin Receptor 2 |
| title_full | Melatonin Regulates Lipid Metabolism in Porcine Cumulus–Oocyte Complexes via the Melatonin Receptor 2 |
| title_fullStr | Melatonin Regulates Lipid Metabolism in Porcine Cumulus–Oocyte Complexes via the Melatonin Receptor 2 |
| title_full_unstemmed | Melatonin Regulates Lipid Metabolism in Porcine Cumulus–Oocyte Complexes via the Melatonin Receptor 2 |
| title_short | Melatonin Regulates Lipid Metabolism in Porcine Cumulus–Oocyte Complexes via the Melatonin Receptor 2 |
| title_sort | melatonin regulates lipid metabolism in porcine cumulus oocyte complexes via the melatonin receptor 2 |
| topic | melatonin receptor lipid metabolism reactive oxygen species cytoplasmic maturation cumulus–oocyte complexes |
| url | https://www.mdpi.com/2076-3921/11/4/687 |
| work_keys_str_mv | AT junxuejin melatoninregulateslipidmetabolisminporcinecumulusoocytecomplexesviathemelatoninreceptor2 AT jingtaosun melatoninregulateslipidmetabolisminporcinecumulusoocytecomplexesviathemelatoninreceptor2 AT chaoqianjiang melatoninregulateslipidmetabolisminporcinecumulusoocytecomplexesviathemelatoninreceptor2 AT hongdicui melatoninregulateslipidmetabolisminporcinecumulusoocytecomplexesviathemelatoninreceptor2 AT yabian melatoninregulateslipidmetabolisminporcinecumulusoocytecomplexesviathemelatoninreceptor2 AT sanghoonlee melatoninregulateslipidmetabolisminporcinecumulusoocytecomplexesviathemelatoninreceptor2 AT lianjinzhang melatoninregulateslipidmetabolisminporcinecumulusoocytecomplexesviathemelatoninreceptor2 AT byeongchunlee melatoninregulateslipidmetabolisminporcinecumulusoocytecomplexesviathemelatoninreceptor2 AT zhonghualiu melatoninregulateslipidmetabolisminporcinecumulusoocytecomplexesviathemelatoninreceptor2 |