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

Poren Kong; Linlin Zhang; Yuyu Guo; Yingli Lu; Dongping Lin

doi:10.1055/s-0034-1368614

Planta Medica, Table of Contents

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

Authors

Poren Kong

¹Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth Peopleʼs Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Linlin Zhang

²Yantai Traditional Chinese Medicine Hospital, Affiliated to Shandong University of Traditional Chinese Medicine, Yantai, China
Yuyu Guo

¹Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth Peopleʼs Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Yingli Lu

¹Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth Peopleʼs Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China
Dongping Lin

¹Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth Peopleʼs Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China

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

Full Text

References

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