木犀草素对3T3-L1细胞成脂分化不同阶段的影响
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摘要
为了研究木犀草素对3T3-L1前脂肪细胞成脂分化过程中各个阶段的作用,文章探讨相关的分子机制,在细胞分化的不同阶段添加20μmol/L木犀草素处理,通过油红O染色和定量聚合酶链式反应(polymerase chain reaction,PCR)检测其对3T3-L1前脂肪细胞脂肪化过程的细节作用。3T3-L1前脂肪细胞成脂分化过程共需8 d,结果表明,木犀草素从细胞分化开始处理8 d可以显著降低其脂滴生成及脂肪化相关基因PPARγ、C/EBPα、Ap2和Fas等的表达,处理2、4、6 d对脂滴生成抑制效果不明显,但可以显著抑制脂肪化相关因子表达,说明木犀草素在3T3-L1细胞的前期分化和后期成熟过程都发挥了重要作用。
To investigate the inhibitory effect of luteolin on the differentiation of 3 T3-L1 preadipocytes at different adipogenic stages and the associated molecular mechanisms, luteolin(20 μmol/L) was added into the medium of 3 T3-L1 during the differentiation at various time points. The levels of adipogenesis were determined using oil red O staining and reverse transcription polymerase chain reaction(RT-PCR). The results showed that the treatment with luteolin for 8 d significantly inhibited lipid droplet generation and adipogenic genes expression, such as C/EBPα, PPARγ, Ap2 and Fas. When 3 T3-L1 cells were treated with luteolin for 2 d, 4 d or 6 d, the lipid droplet generation was not significantly inhibited, although the expression of adipogenic genes was significantly down-regulated. It is shown that luteolin plays an important role during early and terminal differentiation of 3 T3-L1 cells.
To investigate the inhibitory effect of luteolin on the differentiation of 3 T3-L1 preadipocytes at different adipogenic stages and the associated molecular mechanisms, luteolin(20 μmol/L) was added into the medium of 3 T3-L1 during the differentiation at various time points. The levels of adipogenesis were determined using oil red O staining and reverse transcription polymerase chain reaction(RT-PCR). The results showed that the treatment with luteolin for 8 d significantly inhibited lipid droplet generation and adipogenic genes expression, such as C/EBPα, PPARγ, Ap2 and Fas. When 3 T3-L1 cells were treated with luteolin for 2 d, 4 d or 6 d, the lipid droplet generation was not significantly inhibited, although the expression of adipogenic genes was significantly down-regulated. It is shown that luteolin plays an important role during early and terminal differentiation of 3 T3-L1 cells.
引文
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[2] KIM K H,PARK Y.Food components with anti-obesity effect[J].Annu Rev Food Sci Technol,2011,2:237-257.
[3] GURWITZ A A.The spreading worldwide obesity epidemic[J].J Community Health,2014,39(5):827.
[4] TSAI S,CLEMENTE-CASARES X,REVELO X S,et al.Are obesity-related insulin resistance and type 2 diabetes autoimmune diseases?[J].Diabetes,2015,64(6):1886-1897.
[5] KAHN S E,HULL R L,UTZSCHNEIDER K M.Mechanisms linking obesity to insulin resistance and type 2 diabetes[J].Nature,2006,444(7121):840-846.
[6] VAN GAAL L F,MERTENS I L,DE BLOCK C E.Mechanisms linking obesity with cardiovascular disease[J].Nature,2006,444(7121):875-880.
[7] MANDVIWALA T,KHALID U,DESWAL A.Obesity and cardiovascular disease:a risk factor or a risk marker?[J].Curr Atheroscler Rep,2016,18(5):21.
[8] TOPLAK H,HOPPICHLER F,WASCHER T C,et al.Obesity and type 2 diabetes[J].Wien Klin Wochenschr,2016,128(Suppl 2):196-200.
[9] RAY I,MAHATA S K,DE R K.Obesity:an immunometabolic perspective[J].Front Endocrinol (Lausanne),2016,7:157.
[10] KIM J H,CHO J J,PARK Y S.Relationship between sarcopenic obesity and cardiovascular disease risk as estimated by the Framingham risk score[J].J Korean Med Sci,2015,30(3):264-271.
[11] ZEYDA M,STULNING T M.Obesity,inflammation,and insulin resistance:a mini-review[J].Gerontology,2009,55(4):379-386.
[12] ROSEN E D,SPIEGELMAN B M.What we talk about when we talk about fat[J].Cell,2014,156(1/2):20-44.
[13] MAKKI K,FROGUEL P,WOLOWCZUK I.Adipose tissue in obesity-related inflammation and insulin resistance:cells,cytokines,and chemokines[J].ISRN Inflamm,2013,2013:139239-1-12.
[14] GALIC S,OAKHILLl J S,STEINBERG G R.Adipose tissue as an endocrine organ[J].Mol Cell Endocrinol,2010,316(2):129-139.
[15] LOPEZ-LAZARO M.Distribution and biological activities of the flavonoid luteolin [J].Mini-Reviews in Medicinal Chemistry,2009,9(1):31-59.
[16] GARCIA-CLOSAS R,GONZALEZ C A,AGUDO A,et al.Intake of specific carotenoids and flavonoids and risk of gastric cancer in Spain[J].J Org Chem,1999,10(1):71-75.
[17] SUNG J,LEE J.Anti-inflammatory activity of butein and luteolin through suppression of NFκ activation and induction of heme oxygenase-1[J].J Med Food,2015,18(5):557-564.
[18] GALLEANO M,CALABREO V,PRINCE P D,et al.Flavonoids and metabolic syndrome[J].Ann N Y Acad Sci,2012,1259:87-94.
[19] SEELINGER G,MERFORT I,SCHEMPP C.Anti-oxidant,anti-inflammatory and anti-allergic activities of luteolin[J].Planta Medica,2008,74(14):1667-1677.
[20] YANG J T,QIAN L B,ZHANG F J,et al.Cardioprotective effects of luteolin on ischemia/reperfusion injury in diabetic rats are modulated by eNOS and the mitochondrial permeability transition pathway[J].J Cardiovasc Pharmacol,2015,65(4):349-356.
[21] LIN Y,SHI R X,WANG X H,et al.Luteolin,a flavonoid with potentials for cancer prevention and therapy[J].Curr Cancer Drug Targets,2008,8(7):634-646.
[22] PANDURANGAN A K,ESA N M.Luteolin,a bioflavonoid inhibits colorectal cancer through modulation of multiple signaling pathways:a review[J].Asian Pacific Journal of Cancer Prevention,2014,15(14):5501-5508.
[23] XU N,ZHANG L,DONG J,et al.Low-dose diet supplement of a natural flavonoid,luteolin,ameliorates diet-induced obesity and insulin resistance in mice[J].Mol Nutr Food Res,2014,58(6):1258-1268.