Hypoxia-Induced Adipose Lipolysis Requires Fibroblast Growth Factor 21
Fibroblast growth factor 21 (FGF21) is a recently discovered hepatokine that regulates lipid and glucose metabolism and is upregulated in response to numerous physiological and pathological stimuli. Herein, we demonstrate that both physical and chemical hypoxia increase the systemic and hepatic expr...
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.01279/full |
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| author | Guicheng Wu Guicheng Wu Yanlong Liu Yanlong Liu Wenke Feng Xuan An Wenhui Lin Chengwei Tang Chengwei Tang |
| author_facet | Guicheng Wu Guicheng Wu Yanlong Liu Yanlong Liu Wenke Feng Xuan An Wenhui Lin Chengwei Tang Chengwei Tang |
| author_sort | Guicheng Wu |
| collection | DOAJ |
| description | Fibroblast growth factor 21 (FGF21) is a recently discovered hepatokine that regulates lipid and glucose metabolism and is upregulated in response to numerous physiological and pathological stimuli. Herein, we demonstrate that both physical and chemical hypoxia increase the systemic and hepatic expression of FGF21 in mice; by contrast, hypoxia induces a reduction of FGF21 expression in hepatocytes, indicating that hypoxia-induced FGF21 expression is differentially regulated in intact animals and in hepatocytes. Furthermore, we demonstrate that hypoxia treatment increases hormone-sensitive lipase-mediated adipose tissue lipolysis in mice, which is reduced in Fgf21 knockout mice, thereby implying that FGF21 plays a critical role in hypoxia-related adipose lipolysis. Adipose tissue lipolysis causes an increase in the amount of circulating free fatty acids, which leads to the activation of peroxisome proliferators-activated receptor alpha and an increased expression of FGF21 in hepatocytes. We further show that hypoxia-induced elevation of reactive oxygen species, but not the hypoxia-inducible factor, is responsible for the lipolysis and FGF21 expression. In conclusion, our data clearly demonstrate that FGF21 plays a critical role in hypoxia-induced adipose lipolysis, which induces hepatic expression of FGF21. Clarification of hypoxia-regulated FGF21 regulation will enhance our understanding of the pathophysiology of hypoxia-related diseases, such as sleep disorders and metabolic diseases. |
| first_indexed | 2024-12-13T02:51:52Z |
| format | Article |
| id | doaj.art-cfd1086dfeb74aae89e24f1278f3e794 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T02:51:52Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-cfd1086dfeb74aae89e24f1278f3e7942022-12-22T00:02:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-08-011110.3389/fphar.2020.01279561217Hypoxia-Induced Adipose Lipolysis Requires Fibroblast Growth Factor 21Guicheng Wu0Guicheng Wu1Yanlong Liu2Yanlong Liu3Wenke Feng4Xuan An5Wenhui Lin6Chengwei Tang7Chengwei Tang8Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Hepatology, Chongqing University Three Gorges Hospital, Chongqing, ChinaSchool of Mental Health, Wenzhou Medical University, Wenzhou, ChinaZhuji Institute of Biomedicine, School of Pharmaceutical Sciences, Wenzhou Medical University, Shaoxing, ChinaAlcohol Research Center, University of Louisville School of Medicine, Louisville, KY, United StatesDepartment of Hepatology, Chongqing University Three Gorges Hospital, Chongqing, ChinaDepartment of Cardiology, Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Gastroenterology & Hepatology, State Key Laboratory of Biotherapy, Chengdu, ChinaFibroblast growth factor 21 (FGF21) is a recently discovered hepatokine that regulates lipid and glucose metabolism and is upregulated in response to numerous physiological and pathological stimuli. Herein, we demonstrate that both physical and chemical hypoxia increase the systemic and hepatic expression of FGF21 in mice; by contrast, hypoxia induces a reduction of FGF21 expression in hepatocytes, indicating that hypoxia-induced FGF21 expression is differentially regulated in intact animals and in hepatocytes. Furthermore, we demonstrate that hypoxia treatment increases hormone-sensitive lipase-mediated adipose tissue lipolysis in mice, which is reduced in Fgf21 knockout mice, thereby implying that FGF21 plays a critical role in hypoxia-related adipose lipolysis. Adipose tissue lipolysis causes an increase in the amount of circulating free fatty acids, which leads to the activation of peroxisome proliferators-activated receptor alpha and an increased expression of FGF21 in hepatocytes. We further show that hypoxia-induced elevation of reactive oxygen species, but not the hypoxia-inducible factor, is responsible for the lipolysis and FGF21 expression. In conclusion, our data clearly demonstrate that FGF21 plays a critical role in hypoxia-induced adipose lipolysis, which induces hepatic expression of FGF21. Clarification of hypoxia-regulated FGF21 regulation will enhance our understanding of the pathophysiology of hypoxia-related diseases, such as sleep disorders and metabolic diseases.https://www.frontiersin.org/article/10.3389/fphar.2020.01279/fullfibroblast growth factor 21free fatty acidlipolysishormone sensitive lipasehypoxia-inducible factor |
| spellingShingle | Guicheng Wu Guicheng Wu Yanlong Liu Yanlong Liu Wenke Feng Xuan An Wenhui Lin Chengwei Tang Chengwei Tang Hypoxia-Induced Adipose Lipolysis Requires Fibroblast Growth Factor 21 Frontiers in Pharmacology fibroblast growth factor 21 free fatty acid lipolysis hormone sensitive lipase hypoxia-inducible factor |
| title | Hypoxia-Induced Adipose Lipolysis Requires Fibroblast Growth Factor 21 |
| title_full | Hypoxia-Induced Adipose Lipolysis Requires Fibroblast Growth Factor 21 |
| title_fullStr | Hypoxia-Induced Adipose Lipolysis Requires Fibroblast Growth Factor 21 |
| title_full_unstemmed | Hypoxia-Induced Adipose Lipolysis Requires Fibroblast Growth Factor 21 |
| title_short | Hypoxia-Induced Adipose Lipolysis Requires Fibroblast Growth Factor 21 |
| title_sort | hypoxia induced adipose lipolysis requires fibroblast growth factor 21 |
| topic | fibroblast growth factor 21 free fatty acid lipolysis hormone sensitive lipase hypoxia-inducible factor |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.01279/full |
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