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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2018

Open Access 01-12-2018 | Research article

Extract of Paecilomyces hepiali mycelia induces lipolysis through PKA-mediated phosphorylation of hormone-sensitive lipase and ERK-mediated downregulation of perilipin in 3T3-L1 adipocytes

Authors: Mei Ge, Rui Guo, Hai-xia Lou, Wen Zhang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2018

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Abstract

Background

Cordyceps sinensis has been used for centuries in China as one of the most valued herbal medicine and tonic food. Paecilomyces hepiali, a fungal strain isolated from natural C. sinensis, has been used widely as a substitute of C. sinensis in medicine and health food. P. hepiali has been reported to have various pharmaceutical benefits, including triglyceride-lowing activity. However, its effects on triglyceride metabolism in adipocytes remain unknown. The purpose of the present study was to evaluate the effect of P. hepiali mycelia on adipocyte lipolysis and to clarify the underlying mechanisms.

Methods

The fully differentiated 3T3-L1 adipocytes were treated with methanol extract of Paecilomyces hepiali mycelia (PHME). Contents of glycerol released into the culture medium and intracellular triglyceride were measured as indices of lipolysis using glycerol assay kit and Oil red O staining, respectively. Then, effects of PHME on the main lipases or kinases involved in lipolysis regulation were investigated. Protein expression of adipose triglyceride lipase (ATGL) and perilipin, as well as phosphorylation of hormone-sensitive lipase (HSL), AMP-activated protein kinase (AMPK), and mitogen-activated protein kinases (MAPKs) were determined by western blotting. Moreover, nucleosides, important constituents of PHME, were analyzed using high performance liquid chromatography (HPLC).

Results

Treatment with PHME led to a significant increase in glycerol release thereby reduced intracellular triglyceride accumulation in fully differentiated adipocytes. PHME upregulated protein kinase (PK) A-mediated phosphorylation of HSL at serine residues of 563 and 660. Meanwhile, PHME treatment also upregulated phosphorylation of extracellular signal-regulated kinase (ERK), and downregulated the protein level of perilipin. Pretreatment with the PKA inhibitor, H89, blunted the PHME-induced lipolysis and the phosphorylation of HSL (Ser 563 and 660). Moreover, pretreatment with ERK inhibitor, PD98059, weakened the PHME-caused glycerol release and downregulation of perilipin expression. HPLC analysis indicated there were adenosine, cordycepin, uridine and vernine in PHME.

Conclusions

Our results showed that PHME significantly induced lipolysis in 3T3-L1 adipocytes, which is mainly mediated by activation of HSL through PKA pathway and by downregulation of perilipin through activation of ERK pathway.
Appendix
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Metadata
Title
Extract of Paecilomyces hepiali mycelia induces lipolysis through PKA-mediated phosphorylation of hormone-sensitive lipase and ERK-mediated downregulation of perilipin in 3T3-L1 adipocytes
Authors
Mei Ge
Rui Guo
Hai-xia Lou
Wen Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2018
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-018-2389-0

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