Cinchonine Prevents High-Fat-Diet-Induced Obesity through Downregulation of Adipogenesis and Adipose Inflammation

Sung A Jung,Miseon Choi,Taesun Park,Sohee Kim,Rina Yu

doi:10.1155/2012/541204

Sung A Jung, Miseon Choi + Show 3 more

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https://doi.org/10.1155/2012/541204

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Journal: Ppar Research	Publication Date: Jan 1, 2012
Citations: 60	License type: CC BY 3.0

Affiliation: Yonsei University, University of Ulsan

Abstract

Cinchonine (C19H22N2O) is a natural compound of Cinchona bark. Although cinchonine's antiplatelet effect has been reported in the previous study, antiobesity effect of cinchonine has never been studied. The main objective of this study was to investigate whether cinchonine reduces high-fat-diet- (HFD-) induced adipogenesis and inflammation in the epididymal fat tissues of mice and to explore the underlying mechanisms involved in these reductions. HFD-fed mice treated with 0.05% dietary cinchonine for 10 weeks had reduced body weight gain (−38%), visceral fat-pad weights (−26%), and plasma levels of triglyceride, free fatty acids, total cholesterol, and glucose compared with mice fed with the HFD. Moreover, cinchonine significantly reversed HFD-induced downregulations of WNT10b and galanin-mediated signaling molecules and key adipogenic genes in the epididymal adipose tissues of mice. Cinchonine also attenuated the HFD-induced upregulation of proinflammatory cytokines by inhibiting toll-like-receptor-2- (TLR2-) and TLR4-mediated signaling cascades in the adipose tissue of mice. Our findings suggest that dietary cinchonine with its effects on adipogenesis and inflammation may have a potential benefit in preventing obesity.

Highlights

Obesity is defined as a phenotypic manifestation of abnormal or excessive fat accumulation that alters health and increases mortality [1]
The high-fat diet (HFD) upregulates galanin, its receptors, and some molecules in galanin-mediated signaling pathway such as protein kinase C δ (PKCδ) and extracellular signal-regulated kinases (ERKs) that induce the expression of target genes of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) [13]
The total visceral fat pad weights of mice fed on the HFD, which was significantly greater than the weights of normal diet (ND) mice, were reduced when the mice were administered cinchonine

Summary

Introduction

Obesity is defined as a phenotypic manifestation of abnormal or excessive fat accumulation that alters health and increases mortality [1]. The adipose tissue is influenced by diet and genes, as well as by their interactions [2, 3]. WNT signaling repressed adipogenesis by blocking induction of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) [8]. In highfat-diet- (HFD-) induced obesity, the expression of WNT10b is decreased, which further reduces the level of β-catenin transported to nucleus. FOXO1 competes with T-cell factor (TCF) for interaction with β-catenin, thereby inhibiting TCF transcriptional activity and upregulating adipogenesis [9,10,11,12]. The HFD upregulates galanin, its receptors, and some molecules in galanin-mediated signaling pathway such as protein kinase C δ (PKCδ) and extracellular signal-regulated kinases (ERKs) that induce the expression of target genes of PPARγ and C/EBPα [13]

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