AUTHOR=Du Qun , Zhang Shuihong , Li Aiyun , Mohammad Imran S. , Liu Baolin , Li Yanwu 

TITLE=Astragaloside IV Inhibits Adipose Lipolysis and Reduces Hepatic Glucose Production via Akt Dependent PDE3B Expression in HFD-Fed Mice

JOURNAL=Frontiers in Physiology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00015

DOI=10.3389/fphys.2018.00015

ISSN=1664-042X

ABSTRACT=Objective: This study aims to investigate the effect of astragaloside Ⅳ on adipose lipolysis and hepatic gluconeogenesis.
Methods: High-fat diet (HFD) feeding induced adipose dysfunction with enhanced endogenous glucose production in mice. The effects of Astragaloside Ⅳ on lipolysis and hepatic glucose production were investigated.
Results: HFD feeding induced cAMP accumulation through reducing PDE3B expression and activity in adipose tissue. As a result, HFD feeding increased adipose lipolysis in mice. Astragaloside Ⅳ enhanced Akt phosphorylation and promoted Akt binding to PDE3B to preserve PDE3B content, resultantly reducing adipose cAMP accumulation. Knockdown of Akt1/2 diminished the effect of astragaloside Ⅳ on PDE3B induction, indicative of the role of Akt in astragaloside Ⅳ action. As a result from blocking of cAMP/PKA signaling, astragaloside Ⅳ suppressed hormone-sensitive lipase (HSL) activation and inhibited inflammation-associated adipose lipolysis. Moreover, astragaloside Ⅳ reduced ectopic fat deposition in the liver and inhibited FoxO1 activation via regulation of Akt, resultantly restraining excess hepatic glucose production. 
Conclusion: We showed that preserving PDE3B content by Akt is a key regulation to prevent lipolysis. Astragaloside Ⅳ inhibited lipolysis by reducing cAMP accumulation via regulation of Akt/PDE3B, contributing to limiting hepatic lipid deposition and restraining excessive hepatic glucose production.