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Dibenzoylmethane exerts metabolic activity through regulation of AMP-activated protein kinase (AMPK)-mediated glucose uptake and adipogenesis pathways.

Kim N, Kim HM, Lee ES, Lee JO, Lee HJ, Lee SK, Moon JW, Kim JH, Kim JK, Kim SJ, Park SH, Chung CH, Kim HS - PLoS ONE (2015)

Bottom Line: Dibenzoylmethane (DBM) has been shown to exert a variety of beneficial effects on human health.In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis.These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.

ABSTRACT
Dibenzoylmethane (DBM) has been shown to exert a variety of beneficial effects on human health. However, the mechanism of action is poorly understood. In this study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK) and stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake. DBM increased the concentration of intracellular calcium and glucose uptake due to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase inhibitor). DBM stimulated phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which was blocked by pretreatment with compound C, an AMPK inhibitor. The expression of glucose transporter type 4 (GLUT4) was increased by DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat accumulation in the liver and abdomen in mice fed a high-fat diet. In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene, fatty acid synthase (FAS), was suppressed by DBM in an AMPK-dependent manner. These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.

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(A) C2C12 cells were stimulated with different concentrations of DBM for 1 h.The cells were lysed with lysis sample buffer, and the phosphorylation of p38 MAPK was evaluated by western blot using antibodies specific for the phosphorylated protein. The levels of total p38 MAPK were also assessed as a control for protein loading. * p < 0.05, as compared with basal condition. The results are representative of four independent experiments. (B) C2C12 cells were stimulated with 30 μM DBM for 1 h in the presence of compound C (1 μM). The cells were lysed with lysis buffer, and the phosphorylation of p38 MAPK was evaluated by western blot using phosphorylation-specific antibody. The levels of total p38 MAPK were also assessed as a control for protein loading. * p < 0.05, as compared with basal condition. Data are representative of four independent experiments. (C) Myoblast L6 cells were differentiated for 7 days and then incubated with the p38 MAPK inhibitor, SB203580, for 20 min, before cells were incubated with DBM for 18 hours. 2-DG uptake was then measured. *p < 0.05, compared with control. **p < 0.05, compared with DBM-treated cells. This result is representative of four independent experiments.
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pone.0120104.g004: (A) C2C12 cells were stimulated with different concentrations of DBM for 1 h.The cells were lysed with lysis sample buffer, and the phosphorylation of p38 MAPK was evaluated by western blot using antibodies specific for the phosphorylated protein. The levels of total p38 MAPK were also assessed as a control for protein loading. * p < 0.05, as compared with basal condition. The results are representative of four independent experiments. (B) C2C12 cells were stimulated with 30 μM DBM for 1 h in the presence of compound C (1 μM). The cells were lysed with lysis buffer, and the phosphorylation of p38 MAPK was evaluated by western blot using phosphorylation-specific antibody. The levels of total p38 MAPK were also assessed as a control for protein loading. * p < 0.05, as compared with basal condition. Data are representative of four independent experiments. (C) Myoblast L6 cells were differentiated for 7 days and then incubated with the p38 MAPK inhibitor, SB203580, for 20 min, before cells were incubated with DBM for 18 hours. 2-DG uptake was then measured. *p < 0.05, compared with control. **p < 0.05, compared with DBM-treated cells. This result is representative of four independent experiments.

Mentions: To determine which signaling pathway was downstream of AMPK, the effects of DBM on phosphorylation of p38 MAPK were examined. DBM treatment resulted in a concentration-dependent increase in p38 MAPK phosphorylation in C2C12 cells (Fig. 4A). Compound C, an AMPK inhibitor, blocked the DBM-induced increase in p38 MAPK phosphorylation (Fig. 4B). In addition, the DBM-induced increase in 2-DG uptake was abolished by treatment with SB203580, a p38 MAPK inhibitor (Fig. 4C). These results demonstrated that DBM stimulated glucose uptake via AMPK-dependent p38 MAPK activation.


Dibenzoylmethane exerts metabolic activity through regulation of AMP-activated protein kinase (AMPK)-mediated glucose uptake and adipogenesis pathways.

Kim N, Kim HM, Lee ES, Lee JO, Lee HJ, Lee SK, Moon JW, Kim JH, Kim JK, Kim SJ, Park SH, Chung CH, Kim HS - PLoS ONE (2015)

(A) C2C12 cells were stimulated with different concentrations of DBM for 1 h.The cells were lysed with lysis sample buffer, and the phosphorylation of p38 MAPK was evaluated by western blot using antibodies specific for the phosphorylated protein. The levels of total p38 MAPK were also assessed as a control for protein loading. * p < 0.05, as compared with basal condition. The results are representative of four independent experiments. (B) C2C12 cells were stimulated with 30 μM DBM for 1 h in the presence of compound C (1 μM). The cells were lysed with lysis buffer, and the phosphorylation of p38 MAPK was evaluated by western blot using phosphorylation-specific antibody. The levels of total p38 MAPK were also assessed as a control for protein loading. * p < 0.05, as compared with basal condition. Data are representative of four independent experiments. (C) Myoblast L6 cells were differentiated for 7 days and then incubated with the p38 MAPK inhibitor, SB203580, for 20 min, before cells were incubated with DBM for 18 hours. 2-DG uptake was then measured. *p < 0.05, compared with control. **p < 0.05, compared with DBM-treated cells. This result is representative of four independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4355612&req=5

pone.0120104.g004: (A) C2C12 cells were stimulated with different concentrations of DBM for 1 h.The cells were lysed with lysis sample buffer, and the phosphorylation of p38 MAPK was evaluated by western blot using antibodies specific for the phosphorylated protein. The levels of total p38 MAPK were also assessed as a control for protein loading. * p < 0.05, as compared with basal condition. The results are representative of four independent experiments. (B) C2C12 cells were stimulated with 30 μM DBM for 1 h in the presence of compound C (1 μM). The cells were lysed with lysis buffer, and the phosphorylation of p38 MAPK was evaluated by western blot using phosphorylation-specific antibody. The levels of total p38 MAPK were also assessed as a control for protein loading. * p < 0.05, as compared with basal condition. Data are representative of four independent experiments. (C) Myoblast L6 cells were differentiated for 7 days and then incubated with the p38 MAPK inhibitor, SB203580, for 20 min, before cells were incubated with DBM for 18 hours. 2-DG uptake was then measured. *p < 0.05, compared with control. **p < 0.05, compared with DBM-treated cells. This result is representative of four independent experiments.
Mentions: To determine which signaling pathway was downstream of AMPK, the effects of DBM on phosphorylation of p38 MAPK were examined. DBM treatment resulted in a concentration-dependent increase in p38 MAPK phosphorylation in C2C12 cells (Fig. 4A). Compound C, an AMPK inhibitor, blocked the DBM-induced increase in p38 MAPK phosphorylation (Fig. 4B). In addition, the DBM-induced increase in 2-DG uptake was abolished by treatment with SB203580, a p38 MAPK inhibitor (Fig. 4C). These results demonstrated that DBM stimulated glucose uptake via AMPK-dependent p38 MAPK activation.

Bottom Line: Dibenzoylmethane (DBM) has been shown to exert a variety of beneficial effects on human health.In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis.These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.

ABSTRACT
Dibenzoylmethane (DBM) has been shown to exert a variety of beneficial effects on human health. However, the mechanism of action is poorly understood. In this study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK) and stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake. DBM increased the concentration of intracellular calcium and glucose uptake due to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase inhibitor). DBM stimulated phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which was blocked by pretreatment with compound C, an AMPK inhibitor. The expression of glucose transporter type 4 (GLUT4) was increased by DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat accumulation in the liver and abdomen in mice fed a high-fat diet. In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene, fatty acid synthase (FAS), was suppressed by DBM in an AMPK-dependent manner. These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.

Show MeSH
Related in: MedlinePlus