Effects of Capsaicin on Induction of Apoptosis and Inhibition of Adipogenesis in 3T3-L1 Cells

Department of Food Science and Biotechnology, National Chung Hsing University, 250 Kuokuang Road, Taichung 40227, Taiwan.
Journal of Agricultural and Food Chemistry (Impact Factor: 2.91). 04/2007; 55(5):1730-6. DOI: 10.1021/jf062912b
Source: PubMed


Currently, at the beginning of the 21st century, obesity has become the leading metabolic disease in the world. It is a serious health problem in industrialized countries. Previous research has suggested that decreased preadipocyte differentiation and proliferation and decreased lipogenesis are mechanisms to reduce obesity. In the present study, the effects of capsaicin on the induction of apoptosis and inhibition of lipid accumulation in 3T3-L1 preadipocytes and adipocytes were investigated. The results demonstrated that capsaicin decreased cell population growth of 3T3-L1 preadipocytes, assessed with the MTT assay. Flow cytometric analysis of 3T3-L1 preadipocytes exposed to capsaicin showed that apoptotic cells increased in a time- and dose-dependent manner. Treatment with capsaicin decreased the number of normal cells and increased the number of early apoptotic and late apoptotic cells in a dose-dependent manner. The treatment of cells with capsaicin caused the loss of mitochondria membrane potential (delta psi m). The induction of apoptosis in 3T3-L1 preadipocytes by capsaicin was mediated through the activation of caspase-3, Bax, and Bak, and then through the cleavage of PARP and the down-regulation of Bcl-2. Moreover, capsaicin significantly decreased the amount of intracellular triglycerides and glycerol-3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 adipocytes. Capsaicin also inhibited the expression of PPARgamma, C/EBPalpha, and leptin, but induced up-regulation of adiponectin at the protein level. These results demonstrate that capsaicin efficiently induces apoptosis and inhibits adipogenesis in 3T3-L1 preadipocytes and adipocytes.

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    • "Since the anti-adipogenic effect of CAP depends on TRPV1 receptor activation [Hsu and Yen, 2007; Zhang et al., 2007], the effect of BCH on the reduction of lipid accumulation by CAP was used as a positive control for TRPV1 blockage by BCH. In the presence of 25–100 mM BCH, addition of 1 mM CAP did not reduce lipid accumulation, proving the effectiveness of BCH and confirming previous results [Hsu and Yen, 2007; Zhang et al., 2007]. However, addition of 25–100 mM BCH to nonivamide-containing media prevented the anti-adipogenic activity of nonivamide, leading to no reduction in lipid accumulation compared to control treated cells. "
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    ABSTRACT: Red pepper and its major pungent principle, capsaicin, have been shown to be effective anti-obesity agents by reducing energy intake, enhancing energy metabolism, decreasing serum triacylglycerol content, and inhibiting adipogenesis via activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1). However, the binding of capsaicin to the TRPV1 receptor is also responsible for its pungent sensation, strongly limiting its dietary intake. Here, the effects of a less pungent structural capsaicin-analog, nonivamide, on adipogenesis and underlying mechanisms in 3T3-L1 cells were studied. Nonivamide was found to reduce mean lipid accumulation, a marker of adipogenesis, to a similar extent as capsaicin, up to 10.4% (p<0.001). Blockage of the TRPV1 receptor with the specific inhibitor trans-tert-butylcyclohexanol revealed that the anti-adipogenic activity of nonivamide depends, as with capsaicin, on TRPV1 receptor activation. In addition, in cells treated with nonivamide during adipogenesis, protein levels of the pro-adipogenic transcription factor peroxisome-proliferator activated receptor γ (PPARγ) decreased. Results from miRNA microarrays and digital droplet PCR analysis demonstrated an increase in the expression of the miRNA mmu-let-7d-5p, which has been associated with decreased PPARγ levels. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Cellular Biochemistry 02/2015; 116(6). DOI:10.1002/jcb.25052 · 3.26 Impact Factor
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    • "Capsaicin regulation has previously been associated with anti-adipogenesis during differentiation (Bitencourt et al., 2012; Tang and Lane, 2012). Capsaicin-mediated cell death (apoptosis or necrosis) increases in dose-and time-dependent manners according to flow cytometry (Hsu and Yen, 2007). Capsaicin induced apoptosis through a p53-dependent mechanism, ROS, and caspase-3 activation. "
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    ABSTRACT: Capsaicin is a major constituent of hot chili peppers that influences lipid metabolism in animals. In this study, we explored the effects of capsaicin on adipogenic differentiation of bovine bone marrow mesenchymal stem cells (BMSCs) in a dose- and time-dependent manner. The BMSCs were treated with various concentrations of capsaicin (0, 0.1, 1, 5, and 10 μM) for 2, 4, and 6 days. Capsaicin suppressed fat deposition significantly during adipogenic differentiation. Peroxisome proliferator-activated receptor gamma, cytosine-cytosine-adenosine-adenosine-thymidine/enhancer binding protein alpha, fatty acid binding protein 4, and stearoyl-CoA desaturase expression decreased after capsaicin treatment. We showed that the number of apoptotic cells increased in dose- and time-dependent manners. Furthermore, we found that capsaicin increased the expression levels of apoptotic genes, such as B-cell lymphoma 2-associated X protein and caspase 3. Overall, capsaicin inhibits fat deposition by triggering apoptosis.
    Asian Australasian Journal of Animal Sciences 12/2014; 27(12):1783-93. DOI:10.5713/ajas.2014.14720 · 0.54 Impact Factor
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    • "Further, we looked into the gene expression profile of 3T3-L1 pre-adipocytes and adipocytes formed in the presence of capsaicin. Earlier reports suggested that capsaicin affects adipogenesis regulating genes (PPARγ, C/EBPα, aP2) and genes involved in lipid metabolism (HSL, CPTI-α, UCP2, GPDH and leptin) [22], [23]. There are multiple reports suggesting the direct action of capsaicin on PPARγ activity [24], [25]. "
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    ABSTRACT: Objective: Targeting the energy storing white adipose tissue (WAT) by pharmacological and dietary means in order to promote its conversion to energy expending “brite” cell type holds promise as an anti-obesity approach. Present study was designed to investigate/revisit the effect of capsaicin on adipogenic differentiation with special reference to induction of “brite” phenotype during differentiation of 3T3-L1 preadipocytes. Methods: Multiple techniques such as Ca2+ influx assay, Oil Red-O staining, nutrigenomic analysis in preadipocytes and matured adipocytes have been employed to understand the effect of capsaicin at different doses. In addition to in-vitro experiments, in-vivo studies were carried out in high-fat diet (HFD) fed rats treated with resiniferatoxin (RTX) (a TRPV1 agonist) and in mice administered capsaicin. Results: TRPV1 channels are expressed in preadipocytes but not in adipocytes. In preadipocytes, both capsaicin and RTX stimulate Ca2+ influx in dose-dependent manner. This stimulation may be prevented by capsazepine, a TRPV1 antagonist. At lower doses, capsaicin inhibits lipid accumulation and stimulates TRPV1 gene expression, while at higher doses it enhances accumulation of lipids and suppresses expression of its receptor. In doses of 0.1–100 µM, capsaicin promotes expression of major pro-adipogenic factor PPARγ and some of its downstream targets. In concentrations of 1 µM, capsaicin up-regulates anti-adipogenic genes. Low-dose capsaicin treatment of 3T3-L1 preadipocytes differentiating into adipocytes results in increased expression of brown fat cell marker genes. In white adipose of mice, capsaicin administration leads to increase in browning-specific genes. Global TRPV1 ablation (i.p. by RTX administration) leads to increase in locomotor activity with no change in body weight. Conclusion: Our findings suggest the dual modulatory role of capsaicin in adipogenesis. Capsaicin inhibits adipogenesis in 3T3-L1 via TRPV1 activation and induces brown-like phenotype whereas higher doses.
    PLoS ONE 07/2014; 9(7). DOI:10.1371/journal.pone.0103093 · 3.23 Impact Factor
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