Suppression of TNF-α-induced dysregulation of adipocytokine and insulin signaling in 3T3-L1 adipocytes by a diarylheptanoid from Curcuma comosa
Year: 2025
Type: article
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.
Source: ScienceAsia
Institutions: Mahidol University, Ramathibodi Hospital
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4410815807