Research articles
ScienceAsia 51 (2023): 1-10 |doi:
10.2306/scienceasia1513-1874.2023.040
Suppression of TNF-?-induced dysregulation of adipocytokine
and insulin signaling in 3T3-L1 adipocytes by a
diarylheptanoid from Curcuma comosa
Tumnoon Charaslertrangsia, Klodthida Yanukunb, Apichart Suksamrarnc, Pawinee Piyachaturawatb,
Nareerat Sutjaritd,*
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-?) 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-?-induced adipocyte dysfunction using 3T3-L1 mature adipocytes. Exposure to TNF-? (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 ?M inhibited the lipolytic effect of TNF-? in a dose-dependent manner.
TNF-? 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-? 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-?. 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-?.
Download PDF
Downloads Views
| a |
Science Division, Mahidol University International College, Nakhon Pathom 73170 Thailand |
| b |
Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400 Thailand |
| c |
Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240 Thailand |
| d |
Graduate Program in Nutrition, Faculty of Medicine Ramathibodi Hospital, Mahidol University,
Bangkok 10400 Thailand |
* Corresponding author, E-mail: nareerat.sut@mahidol.ac.th
Received 12 Sep 2024, Accepted 26 Feb 2025
|
