title: Monoterpene limonene induces brown fat-like phenotype in 3T3-L1 white adipocytes.
abstract: OBJECTIVE
  Several dietary compounds that are able to induce the brown fat-like phenotype in white adipocytes have been considered for treatment of obesity due to their ability to increase energy expenditure. Here, we report that limonene induces the brown fat-like phenotype in 3T3-L1 adipocytes by increasing expression of brown adipocyte-specific genes and proteins.
  
  
  METHODS
  Limonene-induced browning in white adipocytes was investigated by determining expression levels of brown fat-specific genes and proteins by real-time RT-PCR, immunoblot analysis, and immunocytochemical staining.
  
  
  RESULTS
  Limonene enhanced mitochondrial biogenesis, as evidenced by increased mitochondrial content and immunofluorescent intensity. Limonene also significantly elevated protein levels of HSL, PLIN, p-AMPK, p-ACC, ACO, COX4, CPT1, and CYT C, suggesting its possible role in enhancement of lipolysis and lipid catabolism. Increased expression of PRDM16, UCP1, C/EBPβ, and other brown fat-specific markers by limonene was possibly mediated by activation of β3-adnergenic receptor (β3-AR), as inhibition of β3-AR inhibited up-regulation of brown fat-specific markers. Similarly, limonene-mediated activation of ERK and up-regulation of key brown adipocyte specific markers were eliminated by treatment with ERK antagonist.
  
  
  CONCLUSIONS
  Taken together, these results suggest that limonene induces browning of 3T3-L1 adipocytes via activation of β3-AR and the ERK signaling pathway. In conclusion, our findings suggest that limonene plays a dual modulatory role in induction of the brown adipocyte-like phenotype as well as promotion of lipid metabolism and thus may have potential therapeutic implications for treatment of obesity.
authors.affiliation: Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk 712-714, Republic of Korea.
authors.forename: Jameel
authors.initials: J
authors.lastname: Lone
authors.affiliation: Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk 712-714, Republic of Korea. Electronic address: jwyun@daegu.ac.kr.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Yun
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects*; D052436:Adipose Tissue, White / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation; D053138:Cyclohexenes / Q000494:pharmacology*; D000077222:Limonene; D051379:Mice; D010641:Phenotype; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D053138:Cyclohexenes; D013729:Terpenes; D000077222:Limonene
keywords: 3T3-L1 adipocytes; Anti-obesity; Fat browning; Limonene; UCP1