Altered Gene and Protein Expression in Liver of the Obese Spontaneously Hypertensive/NDmcr-cp Rat

Overview

Journal Nutr Metab (Lond)

Publisher Biomed Central

Date 2012 Sep 25

PMID 22998770

Citations 5

Authors

Jie Chang

Shinji Oikawa

Gaku Ichihara

Yui Nanpei

Yasuhiro Hotta

Yoshiji Yamada

Saeko Tada-Oikawa

Hitoshi Iwahashi

Emiko Kitagawa

Ichiro Takeuchi

Masao Yuda

Sahoko Ichihara

Affiliations

Soon will be listed here.

Abstract

Unlabelled:

Background: It is difficult to study the mechanisms of the metabolic syndrome in humans due to the heterogeneous genetic background and lifestyle. The present study investigated changes in the gene and protein profiles in an animal model of the metabolic syndrome to identify the molecular targets associated with the pathogenesis and progression of obesity related to the metabolic syndrome.

Methods: We extracted mRNAs and proteins from the liver tissues of 6- and 25-week-old spontaneously hypertensive/NIH -corpulent rat SHR/NDmcr-cp (CP), SHR/Lean (Lean) and Wistar Kyoto rats (WKY) and performed microarray analysis and two-dimensional difference in gel electrophoresis (2D-DIGE) linked to a matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS).

Results: The microarray analysis identified 25 significantly up-regulated genes (P < 0.01; log10 > 1) and 31 significantly down-regulated genes (P < 0.01; log10 < -1) in 6- and 25-week-old CP compared with WKY and Lean. Several of these genes are known to be involved in important biological processes such as electron transporter activity, electron transport, lipid metabolism, ion transport, transferase, and ion channel activity. MALDI-TOF/TOF MS identified 31 proteins with ±1.2 fold change (P < 0.05) in 6- and 25-week-old CP, compared with age-matched WKY and Lean. The up-regulated proteins are involved in metabolic processes, biological regulation, catalytic activity, and binding, while the down-regulated proteins are involved in endoplasmic reticulum stress-related unfolded protein response.

Conclusion: Genes with significant changes in their expression in transcriptomic analysis matched very few of the proteins identified in proteomics analysis. However, annotated functional classifications might provide an important reference resource to understand the pathogenesis of obesity associated with the metabolic syndrome.

Citing Articles

Carbonylated Proteins as Key Regulators in the Progression of Metabolic Syndrome.

Kitamura Y, Oikawa S, Chang J, Mori Y, Ichihara G, Ichihara S Antioxidants (Basel). 2023; 12(4).

PMID: 37107219 PMC: 10135001. DOI: 10.3390/antiox12040844.

Proteomics analysis identified peroxiredoxin 2 involved in early-phase left ventricular impairment in hamsters with cardiomyopathy.

Kuzuya K, Ichihara S, Suzuki Y, Inoue C, Ichihara G, Kurimoto S PLoS One. 2018; 13(2):e0192624.

PMID: 29438398 PMC: 5810987. DOI: 10.1371/journal.pone.0192624.

Involvement of oxidative modification of proteins related to ATP synthesis in the left ventricles of hamsters with cardiomyopathy.

Ichihara S, Suzuki Y, Chang J, Kuzuya K, Inoue C, Kitamura Y Sci Rep. 2017; 7(1):9243.

PMID: 28835655 PMC: 5569096. DOI: 10.1038/s41598-017-08546-1.

Differential representation of liver proteins in obese human subjects suggests novel biomarkers and promising targets for drug development in obesity.

Caira S, Iannelli A, Sciarrillo R, Picariello G, Renzone G, Scaloni A J Enzyme Inhib Med Chem. 2017; 32(1):672-682.

PMID: 28274171 PMC: 6009959. DOI: 10.1080/14756366.2017.1292262.

Expression of proteins associated with adipocyte lipolysis was significantly changed in the adipose tissues of the obese spontaneously hypertensive/NDmcr-cp rat.

Chang J, Oikawa S, Iwahashi H, Kitagawa E, Takeuchi I, Yuda M Diabetol Metab Syndr. 2014; 6(1):8.

PMID: 24468282 PMC: 3937142. DOI: 10.1186/1758-5996-6-8.

References

Fall C, Borja J, Osmond C, Richter L, Bhargava S, Martorell R . Infant-feeding patterns and cardiovascular risk factors in young adulthood: data from five cohorts in low- and middle-income countries. Int J Epidemiol. 2010; 40(1):47-62. PMC: 3043278. DOI: 10.1093/ije/dyq155. View

Khor V, Dhir R, Yin X, Ahima R, Song W . Estrogen sulfotransferase regulates body fat and glucose homeostasis in female mice. Am J Physiol Endocrinol Metab. 2010; 299(4):E657-64. PMC: 2957869. DOI: 10.1152/ajpendo.00707.2009. View

Kislinger T, Cox B, Kannan A, Chung C, Hu P, Ignatchenko A . Global survey of organ and organelle protein expression in mouse: combined proteomic and transcriptomic profiling. Cell. 2006; 125(1):173-86. DOI: 10.1016/j.cell.2006.01.044. View

Qiu Y, Michalak M . Transcriptional control of the calreticulin gene in health and disease. Int J Biochem Cell Biol. 2008; 41(3):531-8. DOI: 10.1016/j.biocel.2008.06.020. View

Iwahashi H, Kitagawa E, Suzuki Y, Ueda Y, Ishizawa Y, Nobumasa H . Evaluation of toxicity of the mycotoxin citrinin using yeast ORF DNA microarray and Oligo DNA microarray. BMC Genomics. 2007; 8:95. PMC: 1865386. DOI: 10.1186/1471-2164-8-95. View

Rogers S, Girolami M, Kolch W, Waters K, Liu T, Thrall B . Investigating the correspondence between transcriptomic and proteomic expression profiles using coupled cluster models. Bioinformatics. 2008; 24(24):2894-900. PMC: 4141638. DOI: 10.1093/bioinformatics/btn553. View

Rosato V, Zucchetto A, Bosetti C, Dal Maso L, Montella M, Pelucchi C . Metabolic syndrome and endometrial cancer risk. Ann Oncol. 2010; 22(4):884-889. DOI: 10.1093/annonc/mdq464. View

Puig A, Gilbert H . Protein disulfide isomerase exhibits chaperone and anti-chaperone activity in the oxidative refolding of lysozyme. J Biol Chem. 1994; 269(10):7764-71. View

Szabo E, Feng T, Dziak E, Opas M . Cell adhesion and spreading affect adipogenesis from embryonic stem cells: the role of calreticulin. Stem Cells. 2009; 27(9):2092-102. DOI: 10.1002/stem.137. View

10.

Furukawa A, Oikawa S, Hasegawa-Ishii S, Chiba Y, Kawamura N, Takei S . Proteomic analysis of aging brain in SAMP10 mouse: a model of age-related cerebral degeneration. Mech Ageing Dev. 2010; 131(6):379-88. DOI: 10.1016/j.mad.2010.05.002. View

11.

Ichihara S, Noda A, Nagata K, Obata K, Xu J, Ichihara G . Pravastatin increases survival and suppresses an increase in myocardial matrix metalloproteinase activity in a rat model of heart failure. Cardiovasc Res. 2005; 69(3):726-35. DOI: 10.1016/j.cardiores.2005.08.001. View

12.

Lozyk M, Papp S, Zhang X, Nakamura K, Michalak M, Opas M . Ultrastructural analysis of development of myocardium in calreticulin-deficient mice. BMC Dev Biol. 2006; 6:54. PMC: 1660575. DOI: 10.1186/1471-213X-6-54. View

13.

Totary-Jain H, Naveh-Many T, Riahi Y, Kaiser N, Eckel J, Sasson S . Calreticulin destabilizes glucose transporter-1 mRNA in vascular endothelial and smooth muscle cells under high-glucose conditions. Circ Res. 2005; 97(10):1001-8. DOI: 10.1161/01.RES.0000189260.46084.e5. View

14.

Freimuth R, Raftogianis R, Wood T, Moon E, Kim U, Xu J . Human sulfotransferases SULT1C1 and SULT1C2: cDNA characterization, gene cloning, and chromosomal localization. Genomics. 2000; 65(2):157-65. DOI: 10.1006/geno.2000.6150. View

15.

Hatahet F, Ruddock L . Substrate recognition by the protein disulfide isomerases. FEBS J. 2007; 274(20):5223-34. DOI: 10.1111/j.1742-4658.2007.06058.x. View

16.

Relogio A, Schwager C, Richter A, Ansorge W, Valcarcel J . Optimization of oligonucleotide-based DNA microarrays. Nucleic Acids Res. 2002; 30(11):e51. PMC: 117213. DOI: 10.1093/nar/30.11.e51. View

17.

Ahima R, Stanley T, Khor V, Zanni M, Grinspoon S . Estrogen sulfotransferase is expressed in subcutaneous adipose tissue of obese humans in association with TNF-alpha and SOCS3. J Clin Endocrinol Metab. 2011; 96(7):E1153-8. PMC: 3135195. DOI: 10.1210/jc.2010-2903. View

18.

Yamada Y, Ichihara S, Kato K, Yoshida T, Yokoi K, Matsuo H . Genetic risk for metabolic syndrome: examination of candidate gene polymorphisms related to lipid metabolism in Japanese people. J Med Genet. 2007; 45(1):22-8. DOI: 10.1136/jmg.2007.052415. View

19.

Sakakibara Y, Yanagisawa K, Katafuchi J, Ringer D, Takami Y, Nakayama T . Molecular cloning, expression, and characterization of novel human SULT1C sulfotransferases that catalyze the sulfonation of N-hydroxy-2-acetylaminofluorene. J Biol Chem. 1998; 273(51):33929-35. DOI: 10.1074/jbc.273.51.33929. View

20.

Arnlov J, Ingelsson E, Sundstrom J, Lind L . Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation. 2009; 121(2):230-6. DOI: 10.1161/CIRCULATIONAHA.109.887521. View