Effects of Neohesperidin on the Differentiation of Adipocyte and the Underlying Mechanism in 3T3-L1 Preadipocytes

GUO Lixia; KONG Shuzhen; YIN Zhongyi; ZHENG Xuxu

doi:10.13386/j.issn1002-0306.20201001641

Volume 42 Issue 12

Jun. 2021

Turn off MathJax

Article Contents

Abstract

References

Science and Technology of Food Industry > 2021 > 42(12): 125-132. > DOI: 10.13386/j.issn1002-0306.20201001641

GUO Lixia, KONG Shuzhen, YIN Zhongyi, et al. Effects of Neohesperidin on the Differentiation of Adipocyte and the Underlying Mechanism in 3T3-L1 Preadipocytes [J]. Science and Technology of Food Industry, 2021, 42(12): 125−132. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.20201001641.

Citation:

PDF (1681 KB)

Effects of Neohesperidin on the Differentiation of Adipocyte and the Underlying Mechanism in 3T3-L1 Preadipocytes

Key Laboratory of Natural Medicine Research of Chongqing Education Commission, Environmental and Resources Institute, Chongqing Technology and Business University, Chongqing 400067, China

More Information

Received Date: October 20, 2020
Available Online: April 18, 2021

Graphical Abstract

Abstract

Abstract

This investigation aimed to identify the effects of neohesperidin on the differentiation of adipocyte and the underlying mechanism in 3T3-L1 preadipocytes. The cell viabilities of neohesperidin were detected in 3T3-L1 cells by MTS assay. The intracellular accumulation of lipids was visualized with Oil-red O staining and spectrophotometry analysis. The mRNA of CCAAT/enhancer binding protein α(C/EBPα) and peroxisome proliferators-activated receptorγ(PPARγ), adipogenic-specific genes during adipocyte differentiation, were measured by RT-PCR. Glycogen synthase kinase3β (GSK3β), glycogen synthase (GS) andprotein phosphorylation, the Akt signaling pathway, were analysed by immunoblotting. To confirm this GSK3β effect, 3T3-L1 cells were incubated with neohesperidin and GSK3β inhibitor (LiCl), and the intracellular accumulation of lipids and the level of adipogenic-specific protein were measured.The results showed that, neohesperidin significantly inhibited adipocyte differentiation and intracellular triglyceride formation (P<0.01), activated Akt signaling pathway, and promoted p-Akt and p-gsk3β, significantly inhibited C/EBPα, PPARγ, the expression of AP2 mRNA and protein (P<0.01). These effects were partly reversed by inhibition of GSK3β activity by LiCl. In summary, neohesperidin suppresses adipocyte differentiation via the Akt/GSK3β signaling pathway in 3T3-L1 preadipocytes.
- neohesperidin,
- Akt/GSK3β signaling pathway,
- adipogenic differentiation

FullText(HTML)

References (30)

References

[1]	Elagizi A, Kachur S, Carbone S, et al. A Review of obesity, physical activity, and cardiovascular disease[J]. Current Obesity Reports,2020,9(4):571−581. doi: 10.1007/s13679-020-00403-z
[2]	Dikaiou P, Bjorck L, Adiels M, et al. Obesity, overweight and risk for cardiovascular disease and mortality in young women[J]. European Journal of Preventive Cardiology,2020:2047487320908983. doi: 10.1177/2047487320908983
[3]	Huang M Y, Wang M Y, Lin Y S, et al. The association between metabolically healthy obesity, cardiovascular disease, and all-cause mortality risk in Asia: Asystematic review and meta-analysis[J]. International Journal of Environmental Research and Public Health,2020,17(4):1320. doi: 10.3390/ijerph17041320
[4]	Gao D, Zhang Y L, Yang F Q, et al. The flower of Edgeworthia gardneri (wall.) Meisn. suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes[J]. Journal of Ethnopharmacology,2016,191:379−386. doi: 10.1016/j.jep.2016.06.059
[5]	Rosen E D, Hsu C H, Wang X, et al. C/EBPalpha induces adipogenesis through PPARgamma: A unified pathway[J]. Genes & Development,2002,16(1):22−26.
[6]	Grimes C A, Jope R S. The multifaceted roles of GSK3beta in cellular signaling[J]. Progress in Neurobiology,2001,65:391−426. doi: 10.1016/S0301-0082(01)00011-9
[7]	Ross S E, EricksonR L, Hemati N, et al. Glycogen synthase kinase 3 is an insulin-regulated C/EBPalpha kinase[J]. Molecular and Cellular Biology,1999,19:8433−8441. doi: 10.1128/MCB.19.12.8433
[8]	Castillo J, Benavente O, Delrio J A. Naringin and neohesperidin levels during development of leaves, flower buds, and fruits of Citrus aurantium[J]. Plant Physiology,1992,99(1):67−73. doi: 10.1104/pp.99.1.67
[9]	Zhang J, Fu X, Yang L, et al. Neohesperidin inhibits cardiac remodeling induced by Ang II in vivo and in vitro[J]. Biomedicine Pharmacotherapy,2020,129:110364. doi: 10.1016/j.biopha.2020.110364
[10]	Zhao T, Hu S, Ma P, et al. Neohesperidin suppresses IgE-mediated anaphylactic reactions and mast cell activation via Lyn-PLC-Ca²⁺ pathway[J]. Phytotherapy Research,2019,33(8):2034−2043. doi: 10.1002/ptr.6385
[11]	Guo J, Fang Y, Jiang F, et al. Neohesperidin inhibits TGF-beta1/Smad3 signaling and alleviates bleomycin-induced pulmonary fibrosis in mice[J]. European Journal of Pharmacology,2019,864:172712. doi: 10.1016/j.ejphar.2019.172712
[12]	Guo C, Zhang H, Guan X, et al. The Anti-aging potential of neohesperidin and its synergistic effects with other citrus flavonoids in extending chronological lifespan of Saccharomyces cerevisiae BY4742[J]. Molecules,2019,24(22):4093. doi: 10.3390/molecules24224093
[13]	Gong Y, Dong R, Gao X, et al. Neohesperidin prevents colorectal tumorigenesis by altering the gut microbiota[J]. Pharmacological Research,2019,148:104460. doi: 10.1016/j.phrs.2019.104460
[14]	Xu F, Zang J, Chen D, et al. Neohesperidin induces cellular apoptosis in human breast adenocarcinoma MDA-MB-231 cells via activating the Bcl-2/Bax-mediated signaling pathway[J]. Natural Product Communications,2012,7(11):1475−1478.
[15]	Wang J, Yuan Y, Zhang P, et al. Neohesperidin prevents Abeta25-35-induced apoptosis in primary cultured hippocampal neurons by blocking the S-nitrosylation of protein-disulphide isomerase[J]. Neurochemical Research,2018,43(9):1736−1744. doi: 10.1007/s11064-018-2589-5
[16]	Tan Z, Cheng J, Liu Q, et al. Neohesperidin suppresses osteoclast differentiation, bone resorption and ovariectomised-induced osteoporosis in mice[J]. Molecularand Cellular Endocrinology,2017,439:369−378. doi: 10.1016/j.mce.2016.09.026
[17]	谭桢, 张丹, 程建文, 等. 新橙皮苷对破骨细胞分化影响的实验研究[J]. 微创医学,2018,13(6):719−722.
[18]	Wu H, Liu Y, Chen X, et al. Neohesperidin exerts lipid-regulating effects in vitro and in vivo via fibroblast growth factor 21 and AMP-activated protein kinase/sirtuin type 1/peroxisome proliferator-activated receptor gamma coactivator 1alpha signaling axis[J]. Pharmacology,2017,100(3-4):115−126. doi: 10.1159/000452492
[19]	Han G E, Kang H T, Chung S, et al. Novel neohesperidin dihydrochalcone analogue inhibits adipogenic differentiation of human adipose-derived stem cells through the Nrf2 pathway[J]. International Journal of Molecular Sciences,2018,19(8):2215. doi: 10.3390/ijms19082215
[20]	Chen M, Zhang J, Hu F, et al. Metformin affects the features of a human hepatocellular cell line (HepG2) by regulating macrophage polarization in a co-culture microenviroment[J]. Diabetes Metabolism Research Reviews,2015,31(8):781−789. doi: 10.1002/dmrr.2761
[21]	Choi S S, Cha B Y, Lee Y S, et al. Magnolol enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells[J]. Life Sciences,2009,84(25-26):908−914. doi: 10.1016/j.lfs.2009.04.001
[22]	Zaragosi L E, Wdziekonski B, Fontaine C, et al. Effects of GSK3 inhibitors on in vitro expansion and differentiation of human adipose-derived stem cells into adipocytes[J]. BMC Molecular and Cell Biology, 2008, 9: 11.
[23]	Lee S, Yang W K, Song J H, et al. Anti-obesity effects of 3-hydroxychromone derivative, a novel small-molecule inhibitor of glycogen synthase kinase-3[J]. Biochemical Pharmacology,2013,85(7):965−976. doi: 10.1016/j.bcp.2012.12.023
[24]	郭莉霞, 张永红, 殷钟意, 等. p-辛弗林通过激活AMPK-FoxO1信号通路抑制肝细胞葡萄糖生成[J]. 食品科学,2019,40(5):156−161. doi: 10.7506/spkx1002-6630-20171109-105
[25]	Yun S J, Kim E K, Tucker D F, et al. Isoform-specific regulation of adipocyte differentiation by Akt/protein kinase Balpha[J]. Biochemical and Biophysical Research Communications,2008,371(1):138−143. doi: 10.1016/j.bbrc.2008.04.029
[26]	Motade S A P, Richard A J, Hang H, et al. Transcriptional regulation of adipogenesis[J]. Comprehensive Physiology,2017,7(2):635−674.
[27]	Sakaue H, Ogawa W, Matsumoto M, et al. Posttranscriptional control of adipocyte differentiation through activation of phosphoinositide 3-kinase[J]. Journalof Biological Chemistry,1998,273(44):28945−28952. doi: 10.1074/jbc.273.44.28945
[28]	Xu J, Liao K. Protein kinase B/AKT 1 plays a pivotal role in insulin-like growth factor-1 receptor signaling induced 3T3-L1 adipocyte differentiation[J]. Journalof Biological Chemistry,2004,279(34):35914−35922. doi: 10.1074/jbc.M402297200
[29]	Turk B E. Glycogen synthase kinase-3beta regulation: Another kinase gets in on the AKT[J]. FEBS Letters,2018,592(4):535−536. doi: 10.1002/1873-3468.12995
[30]	Yen C L, Chao W C, Wu C H, et al. Phosphorylation of glycogen synthase kinase-3beta in metabolically abnormal obesity affects immune stimulation-induced cytokine production[J]. International Journal of Obesity,2015,39(2):270−278. doi: 10.1038/ijo.2014.93

Supplements (0)

Cited By

Cited by

Periodical cited type(4)

1.	周春仲，郑伟清，袁晓怡，欧志坚，姜一平. 高良姜二苯庚烷化合物对3T3-L1前脂肪细胞分化的影响和机制研究. 系统医学. 2024(01): 6-9+13 .
2.	陈少影，李晶晶，兰卫. 常用中药有效成分降脂作用研究进展. 中国实验方剂学杂志. 2023(13): 241-253 .
3.	倪伟锋，赵大庆，倪以宇，白竹林，王思明. 人参-丁香醇提物抑制高山被孢霉脂质合成的活性评价. 食品工业科技. 2022(21): 388-395 . 本站查看
4.	周心悦，周逸辰，陈晋，王文骏，刘东红. 胡柚及其苦味黄烷酮对糖脂代谢相关疾病的调节功能研究进展. 中国食品添加剂. 2022(12): 41-49 .