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Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition.

ABSTRACT: 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.

SUBMITTER: Wu Y

PROVIDER: S-EPMC10985025 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Repurposing lansoprazole to alleviate metabolic syndrome <i>via</i> PHOSPHO1 inhibition.

Wu Yingting Y Xin Jiaqi J Li Xinyu X Yang Ting T Liu Yi Y Zhao Yongsheng Y Xie Wen W Jiang Mengxi M

Acta pharmaceutica Sinica. B 20240104 4

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 ...[more]

PMID: 38572109

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Dataset Information

Repurposing lansoprazole to alleviate metabolic syndrome via PHOSPHO1 inhibition.

Publications

Repurposing lansoprazole to alleviate metabolic syndrome <i>via</i> PHOSPHO1 inhibition.

Similar Datasets

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