Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition
© 2024 The Authors..
Drug repurposing offers an efficient approach to therapeutic development. In this study, our bioinformatic analysis first predicted an association between obesity and lansoprazole (LPZ), a commonly prescribed drug for gastrointestinal ulcers. We went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity, insulin resistance, and hepatic steatosis in mice. Treatment with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes, and induced cold tolerance in cold-exposed mice, suggesting the activity of LPZ in promoting adipose thermogenesis and energy metabolism. Mechanistically, LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1 (PHOSPHO1) and produces metabolic benefits in a PHOSPHO1-dependent manner. Our results suggested that LPZ may stimulate adipose thermogenesis by inhibiting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid (2-AG-LPA) to 2-arachidonoylglycerol (2-AG) and reduce the activity of the thermogenic-suppressive cannabinoid receptor signaling. In summary, we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome, and identified a potential metabolic basis by which LPZ improves energy metabolism.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Acta pharmaceutica Sinica. B - 14(2024), 4 vom: 13. Apr., Seite 1711-1725 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Yingting [VerfasserIn] |
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| Links: |
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| Themen: |
Adipose thermogenesis |
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| Anmerkungen: |
Date Revised 05.04.2024 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.apsb.2024.01.001 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370615417 |
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| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2024 The Authors. | ||
| 520 | |a Drug repurposing offers an efficient approach to therapeutic development. In this study, our bioinformatic analysis first predicted an association between obesity and lansoprazole (LPZ), a commonly prescribed drug for gastrointestinal ulcers. We went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity, insulin resistance, and hepatic steatosis in mice. Treatment with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes, and induced cold tolerance in cold-exposed mice, suggesting the activity of LPZ in promoting adipose thermogenesis and energy metabolism. Mechanistically, LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1 (PHOSPHO1) and produces metabolic benefits in a PHOSPHO1-dependent manner. Our results suggested that LPZ may stimulate adipose thermogenesis by inhibiting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid (2-AG-LPA) to 2-arachidonoylglycerol (2-AG) and reduce the activity of the thermogenic-suppressive cannabinoid receptor signaling. In summary, we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome, and identified a potential metabolic basis by which LPZ improves energy metabolism | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adipose thermogenesis | |
| 650 | 4 | |a Cannabinoid receptor signaling | |
| 650 | 4 | |a Drug repurposing | |
| 650 | 4 | |a Energy expenditure | |
| 650 | 4 | |a Lansoprazole | |
| 650 | 4 | |a Metabolic syndrome | |
| 650 | 4 | |a PHOSPHO1 inhibitor | |
| 650 | 4 | |a Proton pump inhibitors | |
| 700 | 1 | |a Xin, Jiaqi |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yongsheng |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Wen |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Mengxi |e verfasserin |4 aut | |
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