Effects of all-trans retinoic acid and oxygen concentration on the proliferation and differentiation of subcutaneous adipocytes in yak
In this study, we investigated the mechanism by which all-trans retinoic acid (ATRA) regulates the hypoxic adaptation of yak subcutaneous adipocytes through a dose-dependent regulation. The effects of different concentrations of ATRA (10 nM−10 μM) on cell proliferation and differentiation, lipid met...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2025.1643818/full |
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| author | Sibinuer Yasenjian Sibinuer Yasenjian Su Shan Su Shan Yuqi Zhe Yuqi Zhe Yuqing Zhang Yuqing Zhang Zhixin Chai Zhixin Chai |
| author_facet | Sibinuer Yasenjian Sibinuer Yasenjian Su Shan Su Shan Yuqi Zhe Yuqi Zhe Yuqing Zhang Yuqing Zhang Zhixin Chai Zhixin Chai |
| author_sort | Sibinuer Yasenjian |
| collection | DOAJ |
| description | In this study, we investigated the mechanism by which all-trans retinoic acid (ATRA) regulates the hypoxic adaptation of yak subcutaneous adipocytes through a dose-dependent regulation. The effects of different concentrations of ATRA (10 nM−10 μM) on cell proliferation and differentiation, lipid metabolism and key gene expression were analyzed by simulating a hypoxic environment (1% O2) in vitro. In the hypoxia model, ATRA showed biphasic regulation: the hypoxic environment inhibited cell survival, while low concentrations of ATRA (10–100 nM) significantly enhanced hypoxic cell survival and repaired lipid droplet accumulation by activating the PCNA/PPAR-γ signaling axis; while high concentrations of ATRA (1–10 μM) induced apoptosis and inhibited differentiation by upregulating BAX and inhibited differentiation, and its toxic effects were exacerbated by the hypoxic environment. In addition, a certain concentration (10–100 nM) of ATRA antagonized the hypoxia-induced HIF-1α pathway and regulated hypoxia-induced metabolic reprogramming via PCNA/PPAR-γ. The study revealed a dose-dependent bidirectional regulatory mechanism of ATRA in the hypoxic adaptation of yak adipocytes, which provides a new perspective for analyzing the energy metabolism strategy of plateau species. |
| format | Article |
| id | doaj-art-48742d9d30644317beb0731a795fca5d |
| institution | Kabale University |
| issn | 2297-1769 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj-art-48742d9d30644317beb0731a795fca5d2025-08-26T04:13:07ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-08-011210.3389/fvets.2025.16438181643818Effects of all-trans retinoic acid and oxygen concentration on the proliferation and differentiation of subcutaneous adipocytes in yakSibinuer Yasenjian0Sibinuer Yasenjian1Su Shan2Su Shan3Yuqi Zhe4Yuqi Zhe5Yuqing Zhang6Yuqing Zhang7Zhixin Chai8Zhixin Chai9Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu, ChinaSichuan Qinghai-Tibet Plateau Herbivore Livestock Engineering Technology Center, Chengdu, ChinaKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu, ChinaSichuan Qinghai-Tibet Plateau Herbivore Livestock Engineering Technology Center, Chengdu, ChinaKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu, ChinaSichuan Qinghai-Tibet Plateau Herbivore Livestock Engineering Technology Center, Chengdu, ChinaKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu, ChinaSichuan Qinghai-Tibet Plateau Herbivore Livestock Engineering Technology Center, Chengdu, ChinaKey Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu, ChinaSichuan Qinghai-Tibet Plateau Herbivore Livestock Engineering Technology Center, Chengdu, ChinaIn this study, we investigated the mechanism by which all-trans retinoic acid (ATRA) regulates the hypoxic adaptation of yak subcutaneous adipocytes through a dose-dependent regulation. The effects of different concentrations of ATRA (10 nM−10 μM) on cell proliferation and differentiation, lipid metabolism and key gene expression were analyzed by simulating a hypoxic environment (1% O2) in vitro. In the hypoxia model, ATRA showed biphasic regulation: the hypoxic environment inhibited cell survival, while low concentrations of ATRA (10–100 nM) significantly enhanced hypoxic cell survival and repaired lipid droplet accumulation by activating the PCNA/PPAR-γ signaling axis; while high concentrations of ATRA (1–10 μM) induced apoptosis and inhibited differentiation by upregulating BAX and inhibited differentiation, and its toxic effects were exacerbated by the hypoxic environment. In addition, a certain concentration (10–100 nM) of ATRA antagonized the hypoxia-induced HIF-1α pathway and regulated hypoxia-induced metabolic reprogramming via PCNA/PPAR-γ. The study revealed a dose-dependent bidirectional regulatory mechanism of ATRA in the hypoxic adaptation of yak adipocytes, which provides a new perspective for analyzing the energy metabolism strategy of plateau species.https://www.frontiersin.org/articles/10.3389/fvets.2025.1643818/fullyaksubcutaneous adipocytesall-trans retinoic acidproliferationdifferentiationhypoxia adaptation |
| spellingShingle | Sibinuer Yasenjian Sibinuer Yasenjian Su Shan Su Shan Yuqi Zhe Yuqi Zhe Yuqing Zhang Yuqing Zhang Zhixin Chai Zhixin Chai Effects of all-trans retinoic acid and oxygen concentration on the proliferation and differentiation of subcutaneous adipocytes in yak Frontiers in Veterinary Science yak subcutaneous adipocytes all-trans retinoic acid proliferation differentiation hypoxia adaptation |
| title | Effects of all-trans retinoic acid and oxygen concentration on the proliferation and differentiation of subcutaneous adipocytes in yak |
| title_full | Effects of all-trans retinoic acid and oxygen concentration on the proliferation and differentiation of subcutaneous adipocytes in yak |
| title_fullStr | Effects of all-trans retinoic acid and oxygen concentration on the proliferation and differentiation of subcutaneous adipocytes in yak |
| title_full_unstemmed | Effects of all-trans retinoic acid and oxygen concentration on the proliferation and differentiation of subcutaneous adipocytes in yak |
| title_short | Effects of all-trans retinoic acid and oxygen concentration on the proliferation and differentiation of subcutaneous adipocytes in yak |
| title_sort | effects of all trans retinoic acid and oxygen concentration on the proliferation and differentiation of subcutaneous adipocytes in yak |
| topic | yak subcutaneous adipocytes all-trans retinoic acid proliferation differentiation hypoxia adaptation |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2025.1643818/full |
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