Monoterpene limonene induces brown fat-like phenotype in 3T3-L1 white adipocytes

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• 作者：Jameel Lone ; Jong Won Yun ; ^{jwyun@daegu.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ACC ; acyl-CoA carboxylase ; ACO ; acyl-coenzyme A oxidase ; AMPK ; AMP-activated protein kinase ; β3-AR ; beta-3 adrenergic receptor ; BAT ; brown adipose tissue ; Cidea ; gene encoding cell death-inducing DFFA-like effector a ; Cited1 ; gene encoding Cbp/p300-interacting transactivator 1 ; CYT C ; cytochrome C ; COX4 ; cytochrome c oxidase subunit 4 ; C/EBP/Cebp ; CCAAT/enhancer-binding protein/encoding gene ; CPT ; carnitine palmitoyltransferase ; Fgf21 ; gene encoding fibroblast growth factor 21 ; HSL ; hormone-sens
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 May 2016
• 年：2016
• 卷：153
• 期：Complete
• 页码：198-206
• 全文大小：1510 K

文摘

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.

Main 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.

Key findings

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.

Significance

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.