Suppression of TNF-α-induced dysregulation of adipocytokine and insulin signaling in 3T3-L1 adipocytes by a diarylheptanoid from Curcuma comosa
3
Issued Date
2025-06-01
Resource Type
ISSN
15131874
Scopus ID
2-s2.0-105009652577
Journal Title
Scienceasia
Volume
51
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scienceasia Vol.51 No.3 (2025)
Suggested Citation
Charaslertrangsi T., Yanukun K., Suksamrarn A., Piyachaturawat P., Sutjarit N. Suppression of TNF-α-induced dysregulation of adipocytokine and insulin signaling in 3T3-L1 adipocytes by a diarylheptanoid from Curcuma comosa. Scienceasia Vol.51 No.3 (2025). doi:10.2306/scienceasia1513-1874.2025.040 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111150
Title
Suppression of TNF-α-induced dysregulation of adipocytokine and insulin signaling in 3T3-L1 adipocytes by a diarylheptanoid from Curcuma comosa
Corresponding Author(s)
Other Contributor(s)
Abstract
Adipocyte and adipose tissue dysfunction are primary defects in obesity and link obesity to metabolic diseases such as insulin resistance and type 2 diabetes mellitus (type 2 DM). Tumor necrosis factor (TNF-α) released from adipose tissue inhibits insulin signaling, thereby, inducing insulin resistance in adipocytes. Here, we investigated the preventive effect of 1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD), a diarylheptanoid from Curcuma comosa, on TNF-α-induced adipocyte dysfunction using 3T3-L1 mature adipocytes. Exposure to TNF-α (10 ng/ml) for 24 h induced lipolysis and decreased triglyceride accumulation in adipocytes, indicating insulin resistance. Pretreatment with DPHD at concentrations of 0.1, 1, and 10 µM inhibited the lipolytic effect of TNF-α in a dose-dependent manner. TNF-α also increased the expression of genes encoded for proinflammatory cytokines, including interleukin 6 (Il6) and resistin (Retn), while it decreased the expression of genes involved in lipolysis and fatty acid oxidation, including perilipin (Plin1) and adiponectin (adipoq). Consistent with increased lipolysis, TNF-α decreased the expression levels of key proteins in the insulin signaling pathway, including insulin receptor substrate-1 (IRS-1), the phosphorylated phosphoinositide 3-kinase (p-PI3K), phosphorylated AKT (p-AKT), and glucose transporter 4 (GLUT4) in adipocytes. However, pretreatment with DPHD attenuated the changes in gene and protein expressions induced by TNF-α. The preventive effect of DPHD was found to be mediated through the downregulation of the nuclear factor NF-kB p65, a key transcriptional regulator of genes encoding pro-inflammatory cytokines. These results suggested the potential role of DPHD in effectively preventing the dysfunction and insulin resistance of adipocytes associated with TNF-α.