Sudachitin and Nobiletin Stimulate Lipolysis via Activation of the cAMP/PKA/HSL Pathway in 3T3-L1 Adipocytes

Polymethoxyflavones are flavonoids that are abundant in citrus fruit peels and have beneficial effects on human health. Previous studies have demonstrated that the polymethoxyflavones, namely sudachitin and nobiletin, ameliorate obesity and diabetes in humans and rodents. Although nobiletin induces...

Full description

Saved in:
Bibliographic Details
Published in:Foods 2023-05, Vol.12 (10), p.1947
Main Authors: Abe, Tomoki, Sato, Tomoyuki, Murotomi, Kazutoshi
Format: Article
Language:English
Subjects:
Adenylate cyclase
adipocyte
Adipocytes
Antibiotics
Bioassays
Bioflavonoids
Body fat
Citrus
Citrus fruits
Cyclic adenylic acid
Cyclic AMP
Cytotoxicity
Diabetes mellitus
Flavones
Flavonoids
Food science
Glycerin
Glycerol
Health aspects
hormone-sensitive lipase
Insulin resistance
Kinases
Lipids
Lipolysis
Metabolism
nobiletin
Obesity
Overweight
Phosphorylation
Protein kinase A
Protein kinases
Proteins
Substrates
sudachitin
Toxicity
Western blotting
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Polymethoxyflavones are flavonoids that are abundant in citrus fruit peels and have beneficial effects on human health. Previous studies have demonstrated that the polymethoxyflavones, namely sudachitin and nobiletin, ameliorate obesity and diabetes in humans and rodents. Although nobiletin induces lipolysis in adipocytes, lipolytic pathway activation by sudachitin has not been clarified in adipocytes. In this study, the effect of sudachitin on lipolysis was elucidated in murine 3T3-L1 adipocytes. Glycerol release into the medium and activation of the cyclic AMP (cAMP)/protein kinase A (PKA)/hormone-sensitive lipase (HSL) pathway was evaluated in 3T3-L1-differentiated adipocytes. Treatment with sudachitin and nobiletin for 24 and 48 h did not induce cytotoxicity at concentrations of up to 50 μM. Sudachitin and nobiletin at concentrations of 30 and 50 μM increased intracellular cAMP and medium glycerol levels in 3T3-L1 adipocytes. Western blotting revealed that sudachitin and nobiletin dose-dependently increased protein levels of phosphorylated PKA substrates and phosphorylated HSL. Sudachitin- and nobiletin-induced glycerol release, phosphorylation of PKA substrates, and HSL phosphorylation were suppressed by pharmacological inhibition of adenylate cyclase and PKA. These findings indicated that sudachitin, similar to nobiletin, exerts anti-obesogenic effects, at least in part through the induction of lipolysis in adipocytes.
ISSN:2304-8158
2304-8158
DOI:10.3390/foods12101947