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Characterisation of atherogenic effects of low carbohydrate, high protein diet (LCHP) in apoE/LDLR−/− mice

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The journal of nutrition, health & aging

Abstract

Introduction

Low Carbohydrate High Protein diet represents a popular strategy to achieve weight loss.

Objective

The aim of this study was to characterize effects of low carbohydrate, high protein diet (LCHP) on atherosclerotic plaque development in brachiocephalic artery (BCA) in apoE/LDLR−/− mice and to elucidate mechanisms of proatherogenic effects of LCHP diet.

Materials and Methods

Atherosclerosis plaques in brachiocephalic artery (BCA) as well as in aortic roots, lipoprotein profile, inflammation biomarkers, expression of SREBP-1 in the liver as well as mortality were analyzed in Control diet (AIN-93G) or LCHP (Low Carbohydrate High Protein) diet fed mice.

Results

Area of atherosclerotic plaques in aortic roots or BCA from LCHP diet fed mice was substantially increased as compared to mice fed control diet and was characterized by increased lipids and cholesterol contents (ORO staining, FT-IR analysis), increased macrophage infiltration (MOMA-2) and activity of MMPs (zymography). Pro-atherogenic phenotype of LCHP fed apoE/LDLR−/− mice was associated with increased plasma total cholesterol concentration, and in LDL and VLDL fractions, increased TG contents in VLDL, and a modest increase in plasma urea. LCHP diet increased SCD-1 index, activated SREBP-1 transcription factor in the liver and triggered acute phase response as evidence by an increased plasma concentration of haptoglobin, CRP or AGP. Finally, in long-term experiment survival of apoE/LDLR−/− mice fed LCHP diet was substantially reduced as compared to their counterparts fed control diet suggesting overall detrimental effects of LCHP diet on health.

Conclusions

The pro-atherogenic effect of LCHP diet in apoE/LDLR−/− mice is associated with profound increase in LDL and VLDL cholesterol, VLDL triglicerides, liver SREBP-1 upregulation, and systemic inflammation.

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References

  1. Toborek M, Henning D. Dietary methionine imbalance, endothelial cell dysfunction and atherosclerosis. Nutr Res 1996;16: 1251–1266

    Article  CAS  Google Scholar 

  2. Biezanowska-Kopec R, Leszczynska T. The effect of methionine supplementation of the AIN-93G semi-synthetic diet on the levels of homocysteine and lipids in experimental rats. JNHA 2012;16: 395–400

    CAS  Google Scholar 

  3. Parikh P, McDaniel MC, Ashen MD, Miller JI, Sorrentino M, Chan V, Blumenthal RS, Sperling LS. Diets and Cardiovascular Disease An Evidence-Based Assessment. J Am Coll Cardiol 2005;45: 1379–1387

    Article  CAS  PubMed  Google Scholar 

  4. Noakes M, Foster PR, Keogh JB, James AP, Mamo JC, Clifton PM. Comparison of isocaloric very low carbohydrate/high saturated fat and high carbohydrate/low saturated fat diets on body composition and cardiovascular risk. Nutr Metab (Lond) 2006;3:7

    Article  Google Scholar 

  5. Merino J, Kones R, Ferré R, Plana N, Girona J, Aragonés G, Ibarretxe D, Heras M, Masana L. Low-carbohydrate, high-protein, high-fat diet alters small peripheral artery reactivity in metabolic syndrome patients. Clin Investig Arterioscler 2014;26:58–65

    Article  PubMed  Google Scholar 

  6. Foo SY, Heller ER., Wykrzykowska J, Sullivan ChJ, Manning-Tobin JJ, Moore KJ, Gerszten RE, Rosenzweig A. Vascular effects of a low-carbohydrate high-protein diet. PNAS 2009;106: 15418–15423.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Kostogrys RB, Franczyk-Zarów M, Maslak E, Gajda M, Mateuszuk L, Jackson ChL, Chlopicki S. Low carbohydrate, high protein diet promotes atherosclerosis in apolipoprotein E/low-density lipoprotein receptor double knockout mice (apoE/LDLR(−/−). Atherosclerosis 2012;223: 327–331

    Article  CAS  PubMed  Google Scholar 

  8. Csányi G, Gajda M, Franczyk-Zarow M, Kostogrys RB, Gwozdz P, Mateuszuk L, Sternak M, Wojcik L, Zalewska T, Walski M, Chlopicki S. Functional Alterations in Endothelial NO, PGI2 and EDHF Pathways in Aorta in ApoE/LDLR−/− Mice Prostaglandins and Other Lipid Mediators 2012;98 (3–4), 107–115

    PubMed  Google Scholar 

  9. Reeves PG, Nielsen FH, Fahey GC. 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 1993;123: 1939–1951

    CAS  PubMed  Google Scholar 

  10. Rambaldi DC, Reschiglian P, Zattonia A, Johann Ch. Enzymatic determination of cholesterol and triglycerides in serum lipoprotein profiles by asymmetrical flow field-flow fractionation with on-line, dual detection. Anal Chim Acta 2009;654: 64–70

    Article  CAS  PubMed  Google Scholar 

  11. Johann Ch, Elsenberg S, Roesch U, Rambaldi DC, Zattoni A, Reschiglian P. A novel approach to improve operation and performance in flow field-flow fractionation. J Chromatogr A 2011;1218: 4126–4131

    Article  CAS  PubMed  Google Scholar 

  12. Khachigian LM. High-Risk Atherosclerotic Plaques: Mechanisms, Imaging, Models, and Therapy. CRC Press, Boca Raton, Chapter 3 Animal models of vulnerable plaque. Lowe HC, Khachigian LM, Kritharies L, Johnson JL pp 2005;35–52

    Google Scholar 

  13. Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, Badimon JJ, Stefanadis C, Moreno P, Pasterkamp G, Fayad Z, Stone PH, Waxman S, Raggi P, Madjid M, Zarrabi A, Burke A, Yuan C, Fitzgerald PJ, Siscovick DS, de Korte CL, Aikawa M, Airaksinen KE, Assmann G, Becker CR, Chesebro JH, Farb A, Galis ZS, Jackson C, Jang IK, Koenig W, Lodder RA, March K, Demirovic J, Navab M, Priori SG, Rekhter MD, Bahr R, Grundy SM, Mehran R, Colombo A, Boerwinkle E, Ballantyne C, Insull W Jr, Schwartz RS, Vogel R, Serruys PW, Hansson GK, Faxon DP, Kaul S, Drexler H, Greenland P, Muller JE, Virmani R, Ridker PM, Zipes DP, Shah PK, Willerson JT. From Vulnerable Plaque to Vulnerable Patient A Call for New Definitions and Risk Assessment Strategies: Part I. Circulation 2003;108: 1664–1672

    Google Scholar 

  14. Wakefield AP, House JD, Ogborn MR, Weiler HA, Aukema HM. A diet with 35 % of energy from protein leads to kidney damage in female Sprague–Dawley rats. Br J Nutr 2011;106: 656–663

    Article  CAS  PubMed  Google Scholar 

  15. Karpe F, Dickmann JR, Frayn KN. Fatty Acids, Obesity, and Insulin Resistance: Time for a Reevaluation. Diabetes 2011;60: 2441–2449

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Sérougne C, Rukaj A. Plasma and lipoprotein cholesterol in rats fed L-amino acidsupplemented diets. Ann Nutr Metab 1983;27: 386–395.

    Article  PubMed  Google Scholar 

  17. Vahouny GV, Adamson I, Chalcarz W, Satchithanandam IS, Muesing R, Klurfeld DM, Tepper SA, Sanghvi A, Kritchevsky D. Effects of Casein and Soy Protein on Hepatic and Serum Lipids and Lipoprotein Lipid Distributions in the Rat. Atherosclerosis 1985;56: 127–137

    Article  CAS  PubMed  Google Scholar 

  18. Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 2003;72: 137–174

    Article  CAS  PubMed  Google Scholar 

  19. Black S, Kushner I, Samols D. C-reactive Proteina. J Biol Chem 2004;279: 48487–48490

    Article  CAS  PubMed  Google Scholar 

  20. Buzello M, Törnig J, Faulhaber J, Ehmke H, Ritz E, Amann K. The apolipoprotein E knockout mouse: a model documenting accelerated atherogenesis in uremia. J Am Soc Nephrol 2003;14: 311–316

    Article  CAS  PubMed  Google Scholar 

  21. Tuttle KR, Puhlman ME, Cooney SK, Short RA. Effects of amino acids and glucagon on renal hemodynamics in type 1 diabetes. Am J Physiol Renal Physiol 2002;282: F103–112.

    Article  Google Scholar 

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Correspondence to Renata B. Kostogrys.

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Kostogrys, R.B., Johann, C., Czyżyńska, I. et al. Characterisation of atherogenic effects of low carbohydrate, high protein diet (LCHP) in apoE/LDLR−/− mice. J Nutr Health Aging 19, 710–718 (2015). https://doi.org/10.1007/s12603-015-0543-7

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  • DOI: https://doi.org/10.1007/s12603-015-0543-7

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