Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 21, Issue 10, Pages 941-947Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2009.07.009
Keywords
Flavonoids; Adipocyte; Peroxisome proliferator-activated receptor gamma; Insulin sensitivity
Funding
- NIDDK NIH HHS [P30 DK050456] Funding Source: Medline
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Obesity and insulin resistance have been linked to a low-grade chronic inflammatory response characterized by increased macrophage infiltration, altered cytokine production and activation of inflammatory signaling pathway in adipose tissue. Pharmacological agents and natural products that are capable of reducing inflammatory activity possess anti-diabetic properties. Luteolin, a naturally occurring flavonoid, has been demonstrated to inhibit lipopolysaccharide-induced tumor necrosis factor-alpha (INF alpha) release and activation of NF-kappa B pathway in macrophages. However, little is known about the mechanism and effect of luteolin on inflammation-related insulin resistance in adipocytes. In this study, we investigated the effect of luteolin on insulin action in 3T3-L1 adipocytes and primary adipose cells. Here we showed that luteolin treatment for 24 h increased the response of glucose uptake to insulin stimulation in 3T3-L1 adipocytes. Our results also demonstrated that luteolin enhanced Akt2 phosphorylation in an insulin-stimulated state. Furthermore, luteolin treatment decreased mRNA levels of TNF alpha, interleukin-6 and MCP-1, while it increased the gene expression of adiponectin and leptin in 3T3-L1 adipocytes and primary mouse adipose cells. Most interestingly, we found that treatment of luteolin markedly enhanced peroxisome proliferator-activated receptor gamma (PPAR gamma) transcriptional activity in 3T3-L1 adipocytes, and luteolin-increased expression of adiponectin and leptin was blocked by GW9662, a PPAR gamma antagonist. Thus, our data suggest that luteolin influences insulin action and production of adipokines/cytokines in adipocytes by activating the PPAR gamma pathway. (C) 2010 Elsevier Inc. All rights reserved.
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