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High-dose Resveratrol Inhibits Insulin Signaling Pathway in 3T3-L1 Adipocytes.

Lee H, Kim JW - J Lifestyle Med (2013)

Bottom Line: We treated differentiated 3T3-L1 adipocytes with resveratrol to observe whether resveratrol is effective at reducing lipid accumulation.Resveratrol treatment after mitotic clonal expansion resulted in decreased lipid accumulation accompanied by reduced fatty acid synthase expression.The results also provide information about in vivo administration dosages and may explain the discrepancy between in vitro and in vivo effects of resveratrol.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Institute of Genetic Science ; Brain Korea 21 Project for Medical Science.

ABSTRACT

Background: Insulin resistance is a major factor in the development of metabolic syndrome and is associated with central obesity and glucose intolerance. Resveratrol, a polyphenol found in fruits, has been shown to improve metabolic conditions. Although it has been widely studied how resveratrol affects metabolism, little is known about how resveratrol regulates lipogenesis with insulin signaling in 3T3-L1 adipocytes.

Methods: We treated differentiated 3T3-L1 adipocytes with resveratrol to observe whether resveratrol is effective at reducing lipid accumulation.

Results: Resveratrol treatment after mitotic clonal expansion resulted in decreased lipid accumulation accompanied by reduced fatty acid synthase expression. Decreased glucose uptake was observed with inhibited GLUT4 translocation in cells treated with 100 μM resveratrol, suggesting that high doses of resveratrol block insulin signaling in adipocytes. Insulin-stimulated Akt phosphorylation is also dose-dependently reduced with resveratrol treatment. Interestingly, Akt phosphorylation is upregulated when cells are treated with long-term low doses of resveratrol, suggesting that only low doses of resveratrol improve metabolic conditions.

Conclusion: High doses of resveratrol block the insulin signaling pathway, thereby reducing glucose uptake and lipid accumulation in vitro. The results also provide information about in vivo administration dosages and may explain the discrepancy between in vitro and in vivo effects of resveratrol.

No MeSH data available.


Related in: MedlinePlus

The effect of resveratrol on glucose transport in 3T3-L1 adipocytes. (A) Resveratrol inhibits glucose uptake in 3T3-L1 adipocytes. 3T3-L1 cells were differentiated into adipocytes as described in Materials and Methods. After 8 days of differentiation, 3T3-L1 cells were pretreated with or without 50 μM resveratrol (RSV 50) or 100 μM resveratrol (RSV 100) for 3 h in the presence or absence of insulin (100 nM). Glucose uptake was measured as described in Materials and Methods. The results represent the means ± SD for two independent assays in triplicate (*p < 0.01; compared with control). (B) After 8 days of differentiation, cells were treated with insulin in the presence or absence of resveratrol (RSV). The treated cells were fixed and immunostained with a GLUT4 antibody and photographed with confocal microscope. Arrows indicate sites of GLUT4 membrane translocation.
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f2-jlm-03-41: The effect of resveratrol on glucose transport in 3T3-L1 adipocytes. (A) Resveratrol inhibits glucose uptake in 3T3-L1 adipocytes. 3T3-L1 cells were differentiated into adipocytes as described in Materials and Methods. After 8 days of differentiation, 3T3-L1 cells were pretreated with or without 50 μM resveratrol (RSV 50) or 100 μM resveratrol (RSV 100) for 3 h in the presence or absence of insulin (100 nM). Glucose uptake was measured as described in Materials and Methods. The results represent the means ± SD for two independent assays in triplicate (*p < 0.01; compared with control). (B) After 8 days of differentiation, cells were treated with insulin in the presence or absence of resveratrol (RSV). The treated cells were fixed and immunostained with a GLUT4 antibody and photographed with confocal microscope. Arrows indicate sites of GLUT4 membrane translocation.

Mentions: It was well documented that insulin stimulates glucose up-take by GLUT4 translocation and lipogenesis [19,20]. We measured 2-deoxy[14C] glucose uptake in 3T3-L1 adipocytes to test whether the effects on mature 3T3-L1 adipocytes are dependent on insulin signaling. Differentiated 3T3-L1 adipocytes (day 8) were treated with or without 50 μM or 100 μM resveratrol for 3 h (Fig. 2A). Compared to the control cells (2 fold-increase of glucose uptake by insulin), glucose uptake in the cells pretreated with 50 and 100 μM resveratrol for a short time (3 h) was reduced by 32% and 51%, respectively.


High-dose Resveratrol Inhibits Insulin Signaling Pathway in 3T3-L1 Adipocytes.

Lee H, Kim JW - J Lifestyle Med (2013)

The effect of resveratrol on glucose transport in 3T3-L1 adipocytes. (A) Resveratrol inhibits glucose uptake in 3T3-L1 adipocytes. 3T3-L1 cells were differentiated into adipocytes as described in Materials and Methods. After 8 days of differentiation, 3T3-L1 cells were pretreated with or without 50 μM resveratrol (RSV 50) or 100 μM resveratrol (RSV 100) for 3 h in the presence or absence of insulin (100 nM). Glucose uptake was measured as described in Materials and Methods. The results represent the means ± SD for two independent assays in triplicate (*p < 0.01; compared with control). (B) After 8 days of differentiation, cells were treated with insulin in the presence or absence of resveratrol (RSV). The treated cells were fixed and immunostained with a GLUT4 antibody and photographed with confocal microscope. Arrows indicate sites of GLUT4 membrane translocation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390751&req=5

f2-jlm-03-41: The effect of resveratrol on glucose transport in 3T3-L1 adipocytes. (A) Resveratrol inhibits glucose uptake in 3T3-L1 adipocytes. 3T3-L1 cells were differentiated into adipocytes as described in Materials and Methods. After 8 days of differentiation, 3T3-L1 cells were pretreated with or without 50 μM resveratrol (RSV 50) or 100 μM resveratrol (RSV 100) for 3 h in the presence or absence of insulin (100 nM). Glucose uptake was measured as described in Materials and Methods. The results represent the means ± SD for two independent assays in triplicate (*p < 0.01; compared with control). (B) After 8 days of differentiation, cells were treated with insulin in the presence or absence of resveratrol (RSV). The treated cells were fixed and immunostained with a GLUT4 antibody and photographed with confocal microscope. Arrows indicate sites of GLUT4 membrane translocation.
Mentions: It was well documented that insulin stimulates glucose up-take by GLUT4 translocation and lipogenesis [19,20]. We measured 2-deoxy[14C] glucose uptake in 3T3-L1 adipocytes to test whether the effects on mature 3T3-L1 adipocytes are dependent on insulin signaling. Differentiated 3T3-L1 adipocytes (day 8) were treated with or without 50 μM or 100 μM resveratrol for 3 h (Fig. 2A). Compared to the control cells (2 fold-increase of glucose uptake by insulin), glucose uptake in the cells pretreated with 50 and 100 μM resveratrol for a short time (3 h) was reduced by 32% and 51%, respectively.

Bottom Line: We treated differentiated 3T3-L1 adipocytes with resveratrol to observe whether resveratrol is effective at reducing lipid accumulation.Resveratrol treatment after mitotic clonal expansion resulted in decreased lipid accumulation accompanied by reduced fatty acid synthase expression.The results also provide information about in vivo administration dosages and may explain the discrepancy between in vitro and in vivo effects of resveratrol.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Institute of Genetic Science ; Brain Korea 21 Project for Medical Science.

ABSTRACT

Background: Insulin resistance is a major factor in the development of metabolic syndrome and is associated with central obesity and glucose intolerance. Resveratrol, a polyphenol found in fruits, has been shown to improve metabolic conditions. Although it has been widely studied how resveratrol affects metabolism, little is known about how resveratrol regulates lipogenesis with insulin signaling in 3T3-L1 adipocytes.

Methods: We treated differentiated 3T3-L1 adipocytes with resveratrol to observe whether resveratrol is effective at reducing lipid accumulation.

Results: Resveratrol treatment after mitotic clonal expansion resulted in decreased lipid accumulation accompanied by reduced fatty acid synthase expression. Decreased glucose uptake was observed with inhibited GLUT4 translocation in cells treated with 100 μM resveratrol, suggesting that high doses of resveratrol block insulin signaling in adipocytes. Insulin-stimulated Akt phosphorylation is also dose-dependently reduced with resveratrol treatment. Interestingly, Akt phosphorylation is upregulated when cells are treated with long-term low doses of resveratrol, suggesting that only low doses of resveratrol improve metabolic conditions.

Conclusion: High doses of resveratrol block the insulin signaling pathway, thereby reducing glucose uptake and lipid accumulation in vitro. The results also provide information about in vivo administration dosages and may explain the discrepancy between in vitro and in vivo effects of resveratrol.

No MeSH data available.


Related in: MedlinePlus