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Dietary Fat Composition Influences Tissue Lipid Profile and Gene Expression in Fischer-344 Rats

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Lipids

Abstract

The AIN-76A diet causes fatty liver in rodents when fed for long periods of time. The aim of this study was to utilize fatty acid analysis and transcriptomics to investigate the effects of different fat sources in the AIN-76A diet on tissue lipid profiles and gene expression in male, weanling Fischer-344 rats. Animals were fed isocaloric diets that differed only in the fat source: (1) corn oil (CO) (2) anhydrous milk fat (AMF), and (3) AMF supplemented with 10 % phospholipids from the milk fat globule membrane (AMF-MFGM). There were no differences in food intake, body weight, growth rate, or body fat composition among the groups, and the fatty acid compositions of red blood cells (RBC), plasma, muscle, and visceral adipose tissues reflected the dietary fat sources. Modifying the fat source resulted in 293 genes differentially regulated in skeletal muscle, 1,124 in adipose, and 831 in liver as determined by analysis of variance (ANOVA). Although tissue fatty acid profiles mostly reflected the diet, there were several quantitative differences in lipid classes in the liver and plasma. The AMF diet resulted in the highest level of hepatic triacylglycerols, but the lowest level in plasma. The CO diet resulted in significant accumulation of hepatic unesterified fatty acids and decreased DGAT expression and activity, a potential trigger for steatohepatitis. These results indicate that the fatty acid composition and presence of polar lipids in the AIN-76A diets have significant effects on lipid partitioning, gene expression, and potentially the development of liver pathology.

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Abbreviations

ACF:

Aberrant crypt foci

AMF:

Anhydrous milk fat

ANOVA:

Analysis of variance

BHT:

Butylated hydroxytoluene

CE:

Cholesteryl esters

CHD:

Coronary heart disease

CO:

Corn oil

FAME:

Fatty acid methyl ester(s)

FFA:

Unesterified fatty acids

HUFA:

Highly unsaturated fatty acid(s)

MFGM:

Milk fat globule membrane

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

PL:

Phospholipid(s)

PUFA:

Polyunsaturated fatty acids

RBC:

Red blood cell(s)

TAG:

Triacylglycerol(s)

TLC:

Thin-layer chromatography

References

  1. Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123(11):1939–1951

    PubMed  CAS  Google Scholar 

  2. Roebuck BD, Wilpone SA, Fifield DS, Yager JD Jr (1979) Hemorrhagic deaths with AIN-76 diet. J Nutr 109(5):924–925

    PubMed  CAS  Google Scholar 

  3. Nguyen HT, Woodard JC (1980) Intranephronic calculosis in rats: an ultrastructural study. Am J Pathol 100(1):39–56

    PubMed  CAS  Google Scholar 

  4. Medinsky MA, Popp JA, Hamm TE, Dent JG (1982) Development of hepatic lesions in male Fischer-344 rats fed AIN-76A purified diet. Toxicol Appl Pharmacol 62(1):111–120

    Article  PubMed  CAS  Google Scholar 

  5. Nutrition A (1980) Second report of the ad hoc committee on standards for nutritional studies. J Nutr 110:1726

    Google Scholar 

  6. Council NR (1995) Nutrient requirements of laboratory animals, vol 4th Revised. National Academy Press, Washington, p 172

    Google Scholar 

  7. Corpet DE, Tache S (2002) Most effective colon cancer chemopreventive agents in rats: a systematic review of aberrant crypt foci and tumor data, ranked by potency. Nutr Cancer 43(1):1–21

    Article  PubMed  CAS  Google Scholar 

  8. Targher G, Day CP, Bonora E (2010) Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 363(14):1341–1350

    Article  PubMed  CAS  Google Scholar 

  9. Bacon BR, Park CH, Fowell EM, McLaren CE (1984) Hepatic steatosis in rats fed diets with varying concentrations of sucrose. Fundam Appl Toxicol 4(5):819–826

    Article  PubMed  CAS  Google Scholar 

  10. Snow DR, Jimenez-Flores R, Ward RE, Cambell J, Young MJ, Nemere I, Hintze KJ (2010) Dietary milk fat globule membrane reduces the incidence of aberrant crypt foci in Fischer-344 rats. J Agric Food Chem 58(4):2157–2163

    Article  PubMed  CAS  Google Scholar 

  11. Jensen RG (1995) Handbook of milk composition: food science and technology international series. Academic, San Diego, p 919

    Google Scholar 

  12. Mcpherson AV, Dash MC, Kitchen BJ (1984) Isolation of bovine-milk fat globule-membrane material from cream without prior removal of caseins and whey proteins. J Dairy Res 51(1):113–121

    Article  CAS  Google Scholar 

  13. MacGibbon A, Taylor M (2006) Composition and structure of bovine milk lipids. In: Fox PF, McSweeney PLH (eds) Advanced dairy chemistry. Springer, New York, pp 1–42

    Google Scholar 

  14. Spitsberg VL (2005) Invited review: bovine milk fat globule membrane as a potential nutraceutical. J Dairy Sci 88:2289–2294

    Article  PubMed  CAS  Google Scholar 

  15. Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226(1):497–509

    PubMed  CAS  Google Scholar 

  16. Curtis JM, Berrigan N, Dauphinee P (2008) The determination of n-3 fatty acid levels in food products containing microencapsulated fish oil using the one-step extraction method. Part 1: measurement in the raw ingredient and in dry powdered foods. J Am Oil Chem Soc 85(4):297–305

    Article  CAS  Google Scholar 

  17. Blazejczyk M, Miron M, Nadon R (2007) FlexArray: a statistical data analysis software for gene expression microarrays. http://genomequebec.mcgill.ca/FlexArray. Accessed 8 Oct 2012

  18. Long AD, Mangalam HJ, Chan BY, Tolleri L, Hatfield GW, Baldi P (2001) Improved statistical inference from DNA microarray data using analysis of variance and a Bayesian statistical framework: analysis of global gene expression in Escherichia coli K12. J Biol Chem 276(23):19937–19944

    Article  PubMed  CAS  Google Scholar 

  19. Hochberg Y, Benjamini Y (1990) More powerful procedures for multiple significance testing. Stat Med 9(7):811–818

    Article  PubMed  CAS  Google Scholar 

  20. Tong W, Cao X, Harris S, Sun H, Fang H, Fuscoe J, Harris A, Hong H, Xie Q, Perkins R, Shi L, Casciano D (2003) ArrayTrack–supporting toxicogenomic research at the US Food and Drug Administration National Center for Toxicological Research. Environ Health Perspect 111(15):1819–1826

    Article  PubMed  CAS  Google Scholar 

  21. Lopez-Parra M, Titos E, Horrillo R, Ferre N, Gonzalez-Periz A, Martinez-Clemente M, Planaguma A, Masferrer J, Arroyo V, Claria J (2008) Regulatory effects of arachidonate 5-lipoxygenase on hepatic microsomal TG transfer protein activity and VLDL-triglyceride and apoB secretion in obese mice. J Lipid Res 49(12):2513–2523

    Article  PubMed  CAS  Google Scholar 

  22. Abramoff MD, Magalhaes PJ, Ram SJ (2004) Image processing with ImageJ. Biophotonics Int 11(7):36–42

    Google Scholar 

  23. Ko JS, Ryu SY, Kim YS, Chung MY, Kang JS, Rho MC, Lee HS, Kim YK (2002) Inhibitory activity of diacylglycerol acyltransferase by tanshinones from the root of Salvia miltiorrhiza. Arch Pharm Res 25(4):446–448

    Article  PubMed  CAS  Google Scholar 

  24. Coleman RA (1992) Diacylglycerol acyltransferase and monoacylglycerol acyltransferase from liver and intestine. Methods Enzymol 209:98–104

    Article  PubMed  CAS  Google Scholar 

  25. McFie PJ, Stone SJ (2011) A fluorescent assay to quantitatively measure in vitro acyl CoA:diacylglycerol acyltransferase activity. J Lipid Res 52(9):1760–1764

    Article  PubMed  CAS  Google Scholar 

  26. Harris WS, Von Schacky C (2004) The omega-3 index: a new risk factor for death from coronary heart disease? Prev Med 39(1):212–220

    Article  PubMed  CAS  Google Scholar 

  27. Lands B (2008) A critique of paradoxes in current advice on dietary lipids. Prog Lipid Res 47(2):77–106

    Article  PubMed  CAS  Google Scholar 

  28. O’Rourke EJ, Soukas AA, Carr CE, Ruvkun G (2009) C. elegans major fats are stored in vesicles distinct from lysosome-related organelles. Cell Metab 10(5):430–435

    Article  PubMed  Google Scholar 

  29. Yamaguchi K, Yang L, McCall S, Huang J, Yu XX, Pandey SK, Bhanot S, Monia BP, Li YX, Diehl AM (2007) Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Hepatology 45(6):1366–1374

    Article  PubMed  CAS  Google Scholar 

  30. Romestaing C, Piquet MA, Bedu E, Rouleau V, Dautresme M, Hourmand-Ollivier I, Filippi C, Duchamp C, Sibille B (2007) Long term highly saturated fat diet does not induce NASH in Wistar rats. Nutr Metab (Lond) 4:4

    Article  Google Scholar 

  31. Li-Hawkins J, Gafvels M, Olin M, Lund EG, Andersson U, Schuster G, Bjorkhem I, Russell DW, Eggertsen G (2002) Cholic acid mediates negative feedback regulation of bile acid synthesis in mice. J Clin Invest 110(8):1191–1200

    PubMed  CAS  Google Scholar 

  32. Gafvels M, Olin M, Chowdhary BP, Raudsepp T, Andersson U, Persson B, Jansson M, Bjorkhem I, Eggertsen G (1999) Structure and chromosomal assignment of the sterol 12alpha-hydroxylase gene (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid of introns. Genomics 56(2):184–196

    Article  PubMed  CAS  Google Scholar 

  33. Noh SK, Koo SI (2004) Milk sphingomyelin is more effective than egg sphingomyelin in inhibiting intestinal absorption of cholesterol and fat in rats. J Nutr 134(10):2611–2616

    PubMed  CAS  Google Scholar 

  34. Kamili A, Wat E, Chung RW, Tandy S, Weir JM, Meikle PJ, Cohn JS (2010) Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids. Nutr Metab (Lond) 7:90

    Article  CAS  Google Scholar 

  35. Wat E, Tandy S, Kapera E, Kamili A, Chung RW, Brown A, Rowney M, Cohn JS (2009) Dietary phospholipid-rich dairy milk extract reduces hepatomegaly, hepatic steatosis and hyperlipidemia in mice fed a high-fat diet. Atherosclerosis 205(1):144–150

    Article  PubMed  CAS  Google Scholar 

  36. Kersten S (2005) Regulation of lipid metabolism via angiopoietin-like proteins. Biochem Soc Trans 33(Pt 5):1059–1062

    PubMed  CAS  Google Scholar 

  37. Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 101(44):15718–15723

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by both a seed grant from the Center for Integrated Biosystems at Utah State University and by the Utah Agricultural Experiment Station and was approved as journal paper number 8290. We are grateful to Dallin Snow for preparing RNA samples for Microarray analysis and Dr. Aaron Olsen and Kent Udy for assistance with animal studies.

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Authors and Affiliations

  1. Nutrition, Dietetics and Food Sciences, Utah State University, 8700 Old Main Hill, Logan, UT, 84322, USA

    Albert L. Zhou, Korry J. Hintze & Robert E. Ward

  2. Department of Agriculture, Dairy Products Technology Center, California Polytechnic State 21 University, San Luis Obispo, CA, 93407, USA

    Rafael Jimenez-Flores

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  1. Albert L. Zhou
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  2. Korry J. Hintze
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  3. Rafael Jimenez-Flores
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  4. Robert E. Ward
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Correspondence to Robert E. Ward.

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Zhou, A.L., Hintze, K.J., Jimenez-Flores, R. et al. Dietary Fat Composition Influences Tissue Lipid Profile and Gene Expression in Fischer-344 Rats. Lipids 47, 1119–1130 (2012). https://doi.org/10.1007/s11745-012-3729-3

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  • DOI: https://doi.org/10.1007/s11745-012-3729-3

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