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Abstract Title:

Luteolin enhances insulin sensitivity via activation of PPARγ transcriptional activity in adipocytes.

Abstract Source:

Pharmacol Res. 2010 Mar;61(3):247-52. Epub 2009 Dec 21. PMID: 19954946

Abstract Author(s):

Li Ding, Daozhong Jin, Xiaoli Chen

Article Affiliation:

Department of Food Science and Nutrition, University of Minnesota - Twin Cites, St. Paul, MN 55108-1038, USA.

Abstract:

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 (TNFalpha) release and activation of NF-kappaB 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 TNFalpha, 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 (PPARgamma) transcriptional activity in 3T3-L1 adipocytes, and luteolin-increased expression of adiponectin and leptin was blocked by GW9662, a PPARgamma antagonist. Thus, our data suggest that luteolin influences insulin action and production of adipokines/cytokines in adipocytes by activating the PPARgamma pathway.

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