Widdrol-induced lipolysis is mediated by PKC and MEK/ERK in 3T3-L1 adipocytes.

Abstract

Obesity is a serious medical condition causing various diseases such as heart disease, type-2 diabetes, and cancer. Fat cells (adipocytes) play an important role in the generation of energy through hydrolysis of lipids they accumulate. Therefore, induction of lipolysis (breakdown of lipids into fatty acids and glycerol), is one of the ways to treat obesity. In the present study, we investigated the lipolytic effect of widdrol in 3T3-L1 adipocytes and its mechanism. Widdrol considerably increased the amount of glycerol released from 3T3-L1 adipocytes into the medium in a time- and dose-dependent manner. To determine the mechanism of this effect, we investigated the alterations in glycerol release and protein expression in 3T3-L1 adipocytes treated with widdrol alone or widdrol and inhibitors of proteins involved in the cAMP-dependent pathway or cAMP-independent PKC-MAPK pathway, which are known to induce lipolysis in adipocytes. The adenylyl cyclase inhibitor SQ-22536, PLA2 inhibitor dexamethasone, PI3K inhibitor wortmannin, and PKA inhibitor H-89, which were used to investigate the involvement of the cAMP-dependent pathway, did not affect the lipolytic effect of widdrol. Widdrol-induced phosphorylation of PKC, MEK, and ERK, which are related to the PKC-MAPK pathway, and their phosphorylation was inhibited by their inhibitors (H-7, U0126, and PD-98059, respectively). Moreover, the increase in glycerol release induced by widdrol was almost completely blocked by PKC, MEK, and ERK inhibitors. These results suggest that widdrol induces lipolysis through activation of the PKC-MEK-ERK pathway.

• Authors: Hyun Young Jeong, Hee Jung Yun, Byung Woo Kim, Eun Woo Lee, Hyun Ju Kwon
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 410 Issue 1-2 Pg. 247-54 (Dec 2015) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 26359088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Obesity Agents
• Benzocycloheptenes
• Protein Kinase Inhibitors
• widdrol
• Protein Kinase C
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase Kinases
• Glycerol

Topics

• 3T3-L1 Cells
• Adipocytes (drug effects, enzymology)
• Animals
• Anti-Obesity Agents (pharmacology)
• Benzocycloheptenes (pharmacology)
• Dose-Response Relationship, Drug
• Enzyme Activation
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
• Glycerol (metabolism)
• Lipolysis (drug effects)
• Mice
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, metabolism)
• Phosphorylation
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Signal Transduction (drug effects)
• Time Factors