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Planta Med 2014; 80(11): 880-886
DOI: 10.1055/s-0034-1368614
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Phillyrin, a Natural Lignan, Attenuates Tumor Necrosis Factor α-Mediated Insulin Resistance and Lipolytic Acceleration in 3T3-L1 Adipocytes

Poren Kong
1   Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth Peopleʼs Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China
,
Linlin Zhang
2   Yantai Traditional Chinese Medicine Hospital, Affiliated to Shandong University of Traditional Chinese Medicine, Yantai, China
,
Yuyu Guo
1   Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth Peopleʼs Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China
,
Yingli Lu
1   Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth Peopleʼs Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China
,
Dongping Lin
1   Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth Peopleʼs Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China
› Author Affiliations
Further Information

Publication History

received 05 January 2014
revised 09 May 2014

accepted 24 May 2014

Publication Date:
04 July 2014 (online)

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Abstract

In obese adipose tissue, tumor necrosis factor-α secreted from macrophages plays an important role in the adipocyte dysfunctions, including insulin resistance, lipolytic acceleration, and changes of adipokines, which promote the development of obesity-related complications. Phillyrin, an active ingredient found in many medicinal plants and certain functional foods, elicits anti-obesity and anti-inflammatory properties in vivo. The aim of the current study was to investigate the role of phillyrin in preventing tumor necrosis factor α-induced insulin resistance or lipolytic acceleration in 3T3-L1 adipocytes. Our results showed that phillyrin partially restored insulin-stimulated 2-DOG uptake, which was reduced by tumor necrosis factor-α, with concomitant restoration in serine phosphorylation of insulin receptor substrate-1 and insulin-stimulated Glut4 translocation to plasma membrane. Phillyrin also dose-dependently prevented tumor necrosis factor α-stimulated adipocyte lipolysis with preserved downregulation of perilipin. The mitogen-activated protein kinases and I kappaB kinase activation was promoted in tumor necrosis factor α-stimulated adipocytes, but pretreatment with 40 µM phillyrin inhibited the phosphorylation of extracellular signal-regulated kinases1/2, stress-activated protein kinase/Jun N-terminal kinase and I kappaB kinase (p < 0.05). Moreover, phillyrin could inhibit the expressions of interleukin-6 and monocyte chemoattractant protein-1 induced by tumor necrosis factor-α. Using transwell coculture method with 3T3-L1 adipocytes and RAW 264.7 macrophages, the enhanced productions of tumor necrosis factor-α and free fatty acids in the medium were significantly reduced by phillyrin (p < 0.05). These results indicate that phillyrin exerts a beneficial effect on adipocyte dysfunctions induced by tumor necrosis factor-α through suppression of the activation of I kappaB kinase and N-terminal kinase. Phillyrin may have the potential to ameliorate the inflammatory changes and insulin resistance in obese adipose tissue.

Key words

phillyrin - 3T3-L1 adipocytes - TNFα - obesity - insulin resistance

Supporting Information

 

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