Affiliation:
1. Laboratory Animal Center of the Academy of Military Medical Sciences, Beijing, 100193, China
2. State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 100193, China
Abstract
Background:
Docosahexaenoic acid-acylated phloridzin (PZ-DHA), a novel polyphenol fatty acid
ester derivative, is synthesized through an acylation reaction of phloridzin (PZ) and docosahexaenoic acid
(DHA). PZ-DHA is more stable than DHA and exhibits higher cellular uptake and bioavailability than PZ.
Objective:
The study aims to investigate the effects of PZ-DHA on insulin resistance in the skeletal muscle and
the related mechanisms; we used palmitic acid (PA)-treated C2C12 myotubes as an insulin resistance model.
Results:
We found that PZ-DHA increased the activity of AMP-activated protein kinase (AMPK) and improved
glucose uptake and mitochondrial function in an AMPK-dependent manner in untreated C2C12 myotubes.
PZ-DHA treatment of the myotubes reversed PA-induced insulin resistance; this was indicated by increases in
glucose uptake and the expression of membrane glucose transporter 4 (Glut4) and phosphorylated Akt. Moreover,
PZ-DHA treatment reversed PA-induced inflammation and oxidative stress. These effects of PZ-DHA were
mediated by AMPK. Furthermore, the increase in AMPK activity, improvement in insulin resistance, and
decrease in inflammatory and oxidative responses after PZ-DHA treatment diminished upon co-treatment with
a liver kinase B1 (LKB1) inhibitor, suggesting that PZ-DHA improved AMPK activity by regulating its
upstream kinase, LKB1.
Conclusion:
The effects of PZ-DHA on insulin resistance in C2C12 myotubes may be mediated by the LKB1-
AMPK signaling pathway. Hence, PZ-DHA is a promising therapeutic agent for insulin resistance in type 2
diabetes.
Funder
National Natural Science Foundation of China
Earmarked Fund for China Agriculture Research System
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
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