Saturated fatty acid induces insulin resistance partially through nucleotide-binding oligomerization domain 1 signaling pathway in adipocytes.
- Author:
Yi-jun ZHOU
;
Yin-si TANG
1
;
Yu-ling SONG
1
;
Ai LI
1
;
Hui ZHOU
1
;
Yan LI
1
Author Information
- Publication Type:Journal Article
- MeSH: Adipocytes; drug effects; metabolism; Animals; Fatty Acids; pharmacology; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; NF-kappa B; physiology; Nod1 Signaling Adaptor Protein; physiology; Signal Transduction; drug effects; Toll-Like Receptor 4; physiology
- From: Chinese Medical Sciences Journal 2013;28(4):211-217
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo investigate the potential role of nucleotide-binding oligomerization domain 1 (NOD1), a component of the innate immune system, in mediating lipid-induced insulin resistance in adipocytes.
METHODSAdipocytes from Toll-like receptor 4 deficiency mice were used for stimulation experiments. The effect of oleate/palmitate mixture on nuclear factor-κB (NF-κB) activation was analyzed by reporter plasmid assay. The release of proinflammatory chemokine/cytokines production was determined by using real-time PCR. Insulin-stimulated glucose uptake was measured by 2-deoxy-D-[3H] glucose uptake assay. Chemokine/cytokine expression and glucose uptake in adipocytes transfected with small interfering RNA (siRNA) targeting NOD1 upon fatty acids treatment were analyzed.
RESULTSOleate/palmitate mixture activated the NF-κB pathway and induced interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 mRNA expressions in adipocytes from mice deficient in Toll-like receptor 4, and these effects were blocked by siRNA targeting NOD1. Furthermore, saturated fatty acids decreased the ability of insulin-stimulated glucose uptake. Importantly, siRNA targeting NOD1 partially reversed saturated fatty acid-induced suppression of insulin-induced glucose uptake.
CONCLUSIONNOD1 might play an important role in saturated fatty acid-induced insulin resistance in adipocytes, suggesting a mechanism by which reduced NOD1 activity confers beneficial effects on insulin action.