Abstract
Cinnamon polyphenol extract (CPE) improves people with insulin resistance. The objective was to investigate CPE and insulin on diacylglycerol acyltransferase (DGAT) gene expression important for lipid biosynthesis and compared it to anti-inflammatory tristetraprolin/zinc finger protein 36 (TTP/ZFP36) gene expression known to be regulated by both agents. Mouse 3T3-L1 adipocytes and RAW264.7 macrophages were treated with insulin and CPE followed by qPCR evaluation of DGAT and TTP mRNA levels. Insulin decreased DGAT1 and DGAT2 mRNA levels in adipocytes but had no effect on DGAT1 and increased DGAT2 mRNA levels 3-fold in macrophages. Insulin increased TTP mRNA levels 3-fold in adipocytes but had no effect in macrophages. CPE effect on DGAT1 gene expression was minimal but increased DGAT2 mRNA levels 2–4 fold in adipocytes and macrophages. CPE increased TTP mRNA levels 2–7 fold in adipocytes and macrophages. We conclude that CPE and insulin exhibited overlapping and independent effects on DGAT and TTP gene expression and suggest that CPE and insulin have profound effects on fat biosynthesis and inflammatory responses.
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Abbreviations
- ARE:
-
AU-rich element
- CPE:
-
cinnamon polyphenol extract
- DGAT:
-
diacylglycerol acyltransferase
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- DMSO:
-
dimethylsulfoxide
- GM-CSF:
-
granulocyte-macrophage colony-stimulating factor
- qPCR:
-
quantitative real-time PCR
- RPL32:
-
ribosomal protein L32
- TAG:
-
triacylglycerols
- TNFα:
-
tumor necrosis factor alpha
- TTP/ZFP36:
-
tristetraprolin/zinc finger protein 36
- UBQLIN:
-
ubiquilin
References
Farese RV Jr, Walther TC (2009) Lipid droplets finally get a little R-E-S-P-E-C-T. Cell 139:855–860
Liu Q, Siloto RM, Lehner R, Stone SJ, Weselake RJ (2012) Acyl-CoA:diacylglycerol acyltransferase: molecular biology, biochemistry and biotechnology. Prog Lipid Res 51:350–377
Cao H (2011) Structure-function analysis of diacylglycerol acyltransferase sequences from 70 organisms. BMC Res Notes 4:249
Zou J, Wei Y, Jako C, Kumar A, Selvaraj G, Taylor DC (1999) The Arabidopsis thaliana TAG1 mutant has a mutation in a diacylglycerol acyltransferase gene. Plant J 19:645–653
Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber J, Eckel RH, Farese RV Jr (2000) Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet 25:87–90
Haas JT, Winter HS, Lim E, Kirby A, Blumenstiel B, DeFelice M, Gabriel S, Jalas C, Branski D, Grueter CA, Toporovski MS, Walther TC, Daly MJ, Farese RV Jr (2012) DGAT1 mutation is linked to a congenital diarrheal disorder. J Clin Invest 122:4680–4684
Burgal J, Shockey J, Lu C, Dyer J, Larson T, Graham I, Browse J (2008) Metabolic engineering of hydroxy fatty acid production in plants: RcDGAT2 drives dramatic increases in ricinoleate levels in seed oil. Plant Biotechnol J 6:819–831
Jako C, Kumar A, Wei Y, Zou J, Barton DL, Giblin EM, Covello PS, Taylor DC (2001) Seed-specific over-expression of an Arabidopsis cDNA encoding a diacylglycerol acyltransferase enhances seed oil content and seed weight. Plant Physiol 126:861–874
Liu L, Shi X, Bharadwaj KG, Ikeda S, Yamashita H, Yagyu H, Schaffer JE, Yu YH, Goldberg IJ (2009) DGAT1 expression increases heart triglyceride content but ameliorates lipotoxicity. J Biol Chem 284:36312–36323
Kamisaka Y, Tomita N, Kimura K, Kainou K, Uemura H (2007) DGA1 (diacylglycerol acyltransferase gene) overexpression and leucine biosynthesis significantly increase lipid accumulation in the Deltasnf2 disruptant of Saccharomyces cerevisiae. Biochem J 408:61–68
Cao H, Sethumadhavan K (2018) Cottonseed extracts and gossypol regulate diacylglycerol acyltransferase gene expression in mouse macrophages. J Agric Food Chem 66:6022–6030
Wells ML, Perera L, Blackshear PJ (2017) An ancient family of RNA-binding proteins: still important! Trends Biochem Sci 42:285–296
Carballo E, Lai WS, Blackshear PJ (1998) Feedback inhibition of macrophage tumor necrosis factor-alpha production by tristetraprolin. Science 281:1001–1005
Taylor GA, Carballo E, Lee DM, Lai WS, Thompson MJ, Patel DD, Schenkman DI, Gilkeson GS, Broxmeyer HE, Haynes BF, Blackshear PJ (1996) A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity 4:445–454
Sauer I, Schaljo B, Vogl C, Gattermeier I, Kolbe T, Muller M, Blackshear PJ, Kovarik P (2006) Interferons limit inflammatory responses by induction of tristetraprolin. Blood 107:4790–4797
Fu M, Blackshear PJ (2017) RNA-binding proteins in immune regulation: a focus on CCCH zinc finger proteins. Nat Rev Immunol 17:130–143
Patial S, Blackshear PJ (2016) Tristetraprolin as a therapeutic target in inflammatory disease. Trends Pharmacol Sci 37:811–821
Cao H, Polansky MM, Anderson RA (2007) Cinnamon extract and polyphenols affect the expression of tristetraprolin, insulin receptor, and glucose transporter 4 in mouse 3T3-L1 adipocytes. Arch Biochem Biophys 459:214–222
Anderson RA, Broadhurst CL, Polansky MM, Schmidt WF, Khan A, Flanagan VP, Schoene NW, Graves DJ (2004) Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. J Agric Food Chem 52:65–70
Boue SM, Daigle KW, Chen MH, Cao H, Heiman ML (2016) Antidiabetic potential of purple and red rice (Oryza sativa L.) bran extracts. J Agric Food Chem 64:5345–5353
Cao H, Tuttle JS, Blackshear PJ (2004) Immunological characterization of tristetraprolin as a low abundance, inducible, stable cytosolic protein. J Biol Chem 279:21489–21499
Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, Vandesompele J, Wittwer CT (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55:611–622
Cao H, Cao F, Klasson KT (2013) Characterization of reference gene expression in tung tree (Vernicia fordii). Ind Crop Prod 50:248–255
Cao H, Cao F, Roussel AM, Anderson RA (2013) Quantitative PCR for glucose transporter and tristetraprolin family gene expression in cultured mouse adipocytes and macrophages. In Vitro Cell Dev Biol Anim 49:759–770
Cao H, Shockey JM (2012) Comparison of TaqMan and SYBR Green qPCR methods for quantitative gene expression in tung tree tissues. J Agric Food Chem 60:12296–12303
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408
Cao H, Urban JF Jr, Anderson RA (2008) Cinnamon polyphenol extract affects immune responses by regulating anti- and proinflammatory and glucose transporter gene expression in mouse macrophages. J Nutr 138:833–840
Cao H, Urban JF Jr, Anderson RA (2008) Insulin increases tristetraprolin and decreases VEGF gene expression in mouse 3T3-L1 adipocytes. Obesity (Silver Spring) 16:1208–1218
Cao H, Anderson RA (2011) Cinnamon polyphenol extract regulates tristetraprolin and related gene expression in mouse adipocytes. J Agric Food Chem 59:2739–2744
Cao H, Qin B, Panickar KS, Anderson RA (2008) Tea and cinnamon polyphenols improve the metabolic syndrome [review]. Agro Food Ind Hi Tech 19:14–17
Qin B, Dawson H, Polansky MM, Anderson RA (2009) Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes. Horm Metab Res 41:516–522
Cao H (2018) Identification of the major diacylglycerol acyltransferase mRNA in mouse adipocytes and macrophages. BMC Biochem 19(1):1–11
Acknowledgements
This work was supported by the USDA-ARS Quality and Utilization of Agricultural Products National Program 306 through Research Project 6054-41000-103-00-D. USDA is an equal opportunity provider and employer.
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This work was supported by the USDA-ARS Quality and Utilization of Agricultural Products National Program 306 through Research Project 6054–41000–103-00-D. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. USDA is an equal opportunity provider and employer.
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Cao, H., Sethumadhavan, K., Li, K. et al. Cinnamon Polyphenol Extract and Insulin Regulate Diacylglycerol Acyltransferase Gene Expression in Mouse Adipocytes and Macrophages. Plant Foods Hum Nutr 74, 115–121 (2019). https://doi.org/10.1007/s11130-018-0709-7
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DOI: https://doi.org/10.1007/s11130-018-0709-7