title: Thiacremonone, a sulfur compound isolated from garlic, attenuates lipid accumulation partially mediated via AMPK activation in 3T3-L1 adipocytes.
abstract: Garlic extracts exert anti-cancer and anti-inflammatory effects. However, the anti-adipogenic effect of garlic-derived compounds remains unclear. In this study, we examined the effect of thiacremonone, a sulfur compound isolated from garlic, on adipocyte differentiation using 3T3-L1 cells. We found that thiacremonone significantly inhibited 3T3-L1 differentiation via down-regulation of adipogenesis-related transcription factors and adipogenic markers. The inhibitory effect mainly occurred at the early phase of differentiation in 3T3-L1 cells. There was no cytotoxic effect of thiacremonone in 3T3-L1 cells and treatment of differentiating 3T3-L1 cells with thiacremonone resulted in AMPK activation, which led to an attenuated expression of acetyl CoA carboxylase-1 (ACC-1), an essential enzyme for the synthesis and usage of fatty acids. Moreover, thiacremonone enhanced the mRNA level of carnitine palmitoyltransferase (CPT-1). The modulating effect of thiacremonone on expressions of genes involved in lipolysis was partially abrogated by treatment with compound C, an AMPK inhibitor. Taken together, these results indicated that thiacremonone-induced AMPK activation, inhibition of ACC-1 expression and concomitant recovery of CPT-1 expression resulted in the suppression of intracellular lipid droplet levels, suggesting that thiacremonone may induce reduction of lipid synthesis and increases in fatty acid oxidation partially mediated via AMPK activation. Thiacremonone may be a promising compound for the treatment of obesity.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong 1, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Lee
authors.forename: Hee Jong
authors.initials: HJ
authors.lastname: Kim
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Ban
authors.forename: Min Chul
authors.initials: MC
authors.lastname: Cho
authors.forename: Heon Sang
authors.initials: HS
authors.lastname: Jeong
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
mesh_terms: D041721:3T3-L1 Cells; D000091162:AMP-Activated Protein Kinase Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D013876:Thiophenes; D014157:Transcription Factors; C524083:thiacremonone; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D000103:Acetyl-CoA Carboxylase