title: Dibenzoylmethane exerts metabolic activity through regulation of AMP-activated protein kinase (AMPK)-mediated glucose uptake and adipogenesis pathways.
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.
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 220-701, South Korea.
authors.forename: Hong Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 220-701, South Korea.
authors.forename: Eun Soo
authors.initials: ES
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Moon
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Joong Kwan
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 220-701, South Korea.
authors.forename: Choon Hee
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul 136-701, Korea.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D050156:Adipogenesis; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D001692:Biological Transport; D020013:Calcium Signaling; D047188:Chalcones / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000209:etiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats
chemical_list: D019440:Anti-Obesity Agents; D047188:Chalcones; C061481:dibenzoylmethane; D055372:AMP-Activated Protein Kinases; D005947:Glucose