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A PDE1 inhibitor reduces adipogenesis in mice via regulation of lipolysis and adipogenic cell signaling

Authors
 Nam-Jun Kim  ;  Jung-Hwan Baek  ;  JinAh Lee  ;  HyeNa Kim  ;  Jun-Kyu Song  ;  Kyung-Hee Chun 
Citation
 Experimental and Molecular Medicine, Vol.51(1) : 5, 2019 
Journal Title
 Experimental and Molecular Medicine 
ISSN
 1226-3613 
Issue Date
2019
Abstract
Vinpocetine, a phosphodiesterase (PDE) type-1 inhibitor, increases cAMP and cGMP levels and is currently used for the management of cerebrovascular disorders, such as stroke, cerebral hemorrhage, and cognitive dysfunctions. In this study, we first determined that vinpocetine effectively suppressed adipogenesis and lipid accumulation. However, we questioned which molecular mechanism is involved because the role of PDE in adipogenesis is still controversial. Vinpocetine decreased adipogenic cell signaling, including the phosphorylation of ERK, AKT, JAK2, and STAT3, and adipokine secretion, including IL-6, IL-10, and IFN-α. Interestingly, vinpocetine increased the phosphorylation of HSL, suggesting the induction of the lipolysis pathway. Moreover, vinpocetine increased UCP1 expression via increasing cAMP and PKA phosphorylation. The administration of vinpocetine with a normal-chow diet (NFD) or a high-fat diet (HFD) in mice attenuated body weight gain in mice fed both the NFD and HFD. These effects were larger in the HFD-fed mice, without a difference in food intake. Vinpocetine drastically decreased fat weight and adipocyte cell sizes in gonadal and inguinal white adipose tissues and in the liver in both diet groups. Serum triacylglycerol levels and fasting blood glucose levels were reduced by vinpocetine treatment. This study suggested that vinpocetine prevents adipocyte differentiation through the inhibition of adipogenesis-associated cell signaling in the early stages of adipogenesis. Moreover, upregulating cAMP levels leads to an increase in lipolysis and UCP1 expression and then inhibits lipid accumulation. Therefore, we suggest that vinpocetine could be an effective agent for treating obesity, as well as improving cognition and cardiovascular function in older individuals.
Files in This Item:
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DOI
10.1038/s12276-018-0198-7
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
백정환(Baek, Jung Hwan) ORCID logo https://orcid.org/0000-0002-2250-1557
전경희(Chun, Kyung Hee) ORCID logo https://orcid.org/0000-0002-9867-7321
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/167348
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