title: Phillyrin, a natural lignan, attenuates tumor necrosis factor α-mediated insulin resistance and lipolytic acceleration in 3T3-L1 adipocytes.
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.
authors.affiliation: Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Poren
authors.initials: P
authors.lastname: Kong
authors.affiliation: Yantai Traditional Chinese Medicine Hospital, Affiliated to Shandong University of Traditional Chinese Medicine, Yantai, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Endocrine and Metabolic Diseases, Laboratory of Endocrine and Metabolic Diseases, Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Dongping
authors.initials: D
authors.lastname: Lin
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D051550:I-kappa B Kinase / Q000378:metabolism; D007333:Insulin Resistance; D017705:Lignans / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D009765:Obesity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005960:Glucosides; D017705:Lignans; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase; D005947:Glucose; C075528:phillyrin