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

• Published in: PloS one 2015-03, Vol.10 (3), p.e0120104-e0120104
• Main Authors: Kim, Nami, Kim, Hong Min, Lee, Eun Soo, Lee, Jung Ok, Lee, Hye Jeong, Lee, Soo Kyung, Moon, Ji Wook, Kim, Ji Hae, Kim, Joong Kwan, Kim, Su Jin, Park, Sun Hwa, Chung, Choon Hee, Kim, Hyeon Soo
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Acetyl-CoA carboxylase; Adipocytes; Adipogenesis; AMP; AMP-activated protein kinase; AMP-Activated Protein Kinases - physiology; Animals; Anti-Obesity Agents - pharmacology; Biological Transport; Body weight gain; Ca2+/calmodulin-dependent protein kinase; Calcium; Calcium (intracellular); Calcium influx; Calcium Signaling; Calcium-binding protein; Calmodulin; Cancer; Cell cycle; Chalcones - pharmacology; Diabetes; Diet, High-Fat - adverse effects; Drug Evaluation, Preclinical; Enzyme inhibitors; Fatty acid synthesis; Fatty acids; Fatty-acid synthase; Gene expression; Glucose; Glucose - metabolism; Glucose transporter; Health aspects; High fat diet; Immunoglobulins; Inhibition; Inhibitors; Insulin resistance; Internal medicine; Kinases; Liver; MAP kinase; Medicine; Metabolism; Mice; Muscles; Musculoskeletal system; Obesity; Obesity - drug therapy; Obesity - etiology; Phosphorylation; Physicians; Physiological aspects; Protein kinase inhibitors; Protein kinases; Protein Processing, Post-Translational; Proteins; Rats; Rodents; siRNA; Skeletal muscle; Translocation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0120104

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.