Journal Article

Hydroxytyrosol stimulates lipolysis via A-kinase and extracellular signal-regulated kinase activation in 3T3-L1 adipocytes

Drira, Riadh, Sakamoto, Kazuichi

2014

Overview

Purpose The principal function of the adipose tissue is the storage of energy in the form of triglyceride through the process of adipogenesis, as well as the provision of the stored energy through lipolysis. In the present study, we investigated the effect of hydroxytyrosol on lipolysis in 3T3-L1 adipocytes. Methods 3T3-L1 adipocytes, used as in vitro model in this study, were treated with several concentration of hydroxytyrosol. Glycerol release was measured to identify the lipolytic rate activation. All factors activation and expression were carried out via Western blotting and qRT-PCR. Results Our results showed that hydroxytyrosol, over a range of concentrations, attenuated triglyceride accumulation and stimulated glycerol release in fully differentiated adipocytes in a dose- and time-dependent manner. Moreover, hydroxytyrosol had no effect on adipocyte viability. To understand the mechanism underlying hydroxytyrosol-stimulated lipolysis, we used inhibitors of PKA, PKC, PKG, ERK1/2, and nitric oxide production. Pretreatment with a PKA inhibitor (Rp-cAMPs) and an ERK1/2 inhibitor (U0126) significantly attenuated hydroxytyrosol-stimulated lipolysis. In contrast, a PKC inhibitor (Calphostin C), 2 PKG inhibitors (KT 5823 and Rp-cGMPs), and a nitric oxide inhibitor (S-ethyl ITU) had no effect on hydroxytyrosol-stimulated lipolysis. Over the same range of concentrations, hydroxytyrosol downregulated the expression of adipose triglyceride lipase, hormone sensitive lipase (HSL), and adipogenesis-related transcription factors PPARγ and C/EBPα. In addition, hydroxytyrosol increased the phosphorylation rate of HSL at Ser563 and Ser660, as well as perilipin and ERK phosphorylation. Conclusion Hydroxytyrosol induced lipolysis in 3T3-L1 adipocytes via the activation of PKA and ERK1/2 pathway.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: 3T3-L1 Cells / adipocytes / Adipocytes, White / Adipocytes, White - drug effects / Adipocytes, White - enzymology / Adipocytes, White - metabolism / adipose tissue / adverse effects / analogs & derivatives / Animals / antagonists & inhibitors / Antioxidants / Antioxidants - adverse effects / Antioxidants - chemistry / Antioxidants - pharmacology / Biological and medical sciences / cAMP-dependent protein kinase / Cell Survival / Cell Survival - drug effects / cGMP-dependent protein kinase / Chemistry / Chemistry and Materials Science / Cyclic AMP-Dependent Protein Kinases / Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors / Cyclic AMP-Dependent Protein Kinases - chemistry / Cyclic AMP-Dependent Protein Kinases - metabolism / drug effects / energy / Enzyme Activation / Enzyme Activation - drug effects / enzymology / Feeding. Feeding behavior / Fundamental and applied biological sciences. Psychology / gene expression regulation / Gene Expression Regulation, Enzymologic / Gene Expression Regulation, Enzymologic - drug effects / genetics / glycerol / Glycerol - metabolism / Kinetics / Lipase / Lipase - antagonists & inhibitors / Lipase - genetics / Lipase - metabolism / lipogenesis / lipolysis / Lipolysis - drug effects / MAP Kinase Signaling System / MAP Kinase Signaling System - drug effects / metabolism / Mice / mitogen-activated protein kinase / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors / Mitogen-Activated Protein Kinase 1 - chemistry / Mitogen-Activated Protein Kinase 1 - metabolism / Mitogen-Activated Protein Kinase 3 / Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors / Mitogen-Activated Protein Kinase 3 - chemistry / Mitogen-Activated Protein Kinase 3 - metabolism / nitric oxide / Nutrition / Original Contribution / pharmacology / Phenylethyl Alcohol / Phenylethyl Alcohol - adverse effects / Phenylethyl Alcohol - analogs & derivatives / Phenylethyl Alcohol - antagonists & inhibitors / Phenylethyl Alcohol - pharmacology / phosphorylation / Phosphorylation - drug effects / protein kinase C / Protein Kinase Inhibitors / Protein Kinase Inhibitors - pharmacology / Protein Processing, Post-Translational / Protein Processing, Post-Translational - drug effects / reverse transcriptase polymerase chain reaction / Sterol Esterase / Sterol Esterase - genetics / Sterol Esterase - metabolism / transcription factors / triacylglycerol lipase / triacylglycerols / Triglycerides / Triglycerides - metabolism / Vertebrates: anatomy and physiology, studies on body, several organs or systems / viability / Western blotting