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Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet

      Abstract

      Introduction

      Low-carbohydrate diets (LCD) efficiently induce weight loss and favorably affect plasma lipids, however, the effect of LCD on atherosclerosis is still argued.

      Objective

      To evaluate the effect of LCD on the prevention of atherosclerosis.

      Methods

      Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25 g/100 g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined.

      Results

      LDL cholesterol was lower in the LCD compared to the LFD group (71.9 ± 34.8 vs. 81.7 ± 26.9 mg/dL; p = 0.039). Aortic cholesterol was also lower in the LCD (4.98 ± 1.3 mg/g) compared to the LFD group (6.68 ± 2.0 mg/g); p < 0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p = 0.045). There was a positive correlation (r = 0.63, p = 0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r = −0.05, p = 0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p < 0.05) and they were correlated with the decreases in oxLDL in aorta.

      Conclusion

      These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis.

      Keywords

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      References

        • Volek J.S.
        • Feinman R.D.
        Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction.
        Nutr Metab (Lond). 2005; 2: 31
        • Samaha F.F.
        • Iqbal N.
        • Seshadri P.
        • et al.
        A low-carbohydrate as compared with a low-fat diet in severe obesity.
        N Engl J Med. 2003; 348: 2074-2081
        • Halton T.L.
        • Willett W.C.
        • Liu S.
        • et al.
        Low-carbohydrate-diet score and the risk of coronary heart disease in women.
        N Engl J Med. 2006; 355: 1991-2002
        • Bantle J.P.
        • Wylie-Rosett J.
        • Albright A.L.
        • et al.
        Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association.
        Diabetes Care. 2008; 31: S61-78
        • Brehm B.J.
        • Seeley R.J.
        • Daniels S.R.
        • D’Alessio D.A.
        A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women.
        J Clin Endocrinol Metab. 2003; 88: 1617-1623
        • Yancy Jr., W.S.
        • Olsen M.K.
        • Guyton J.R.
        • Bakst R.P.
        • Westman E.C.
        A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial.
        Ann Intern Med. 2004; 140: 769-777
        • Stern L.
        • Iqbal N.
        • Seshadri P.
        • et al.
        The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial.
        Ann Intern Med. 2004; 140: 778-785
        • Fernandez M.L.
        • Sun D.M.
        • Montano C.
        • McNamara D.J.
        Carbohydrate-fat exchange and regulation of hepatic cholesterol and plasma lipoprotein metabolism in the guinea pig.
        Metabolism. 1995; 44: 855-864
        • Sharman M.J.
        • Fernandez M.L.
        • Zern T.L.
        • et al.
        Replacing dietary carbohydrate with protein and fat decreases the concentrations of small LDL and the inflammatory response induced by atherogenic diets in the guinea pig.
        J Nutr Biochem. 2008; 19: 732-738
        • Leite J.O.
        • Vaishnav U.
        • Puglisi M.
        • et al.
        A-002 (Varespladib), a phospholipase A2 inhibitor, reduces atherosclerosis in guinea pigs.
        BMC Cardiovasc Disord. 2009; 9: 7
        • West K.L.
        • Zern T.L.
        • Butteiger D.N.
        • Keller B.T.
        • Fernandez M.L.
        SC-435, an ileal apical sodium co-dependent bile acid transporter (ASBT) inhibitor lowers plasma cholesterol and reduces atherosclerosis in guinea pigs.
        Atherosclerosis. 2003; 171: 201-210
        • Fernandez M.L.
        Guinea pigs as models for cholesterol and lipoprotein metabolism.
        J Nutr. 2001; 131: 10-20
        • Fernandez M.L.
        • Volek J.S.
        Guinea pigs: a suitable animal model to study lipoprotein metabolism, atherosclerosis and inflammation.
        Nutr Metab (Lond). 2006; 3: 17
        • Volek J.S.
        • Sharman M.J.
        • Gomez A.L.
        • et al.
        Comparison of a very low-carbohydrate and low-fat diet on fasting lipids, LDL subclasses, insulin resistance, and postprandial lipemic responses in overweight women.
        J Am Coll Nutr. 2004; 23: 177-184
        • Sharman M.J.
        • Kraemer W.J.
        • Love D.M.
        • et al.
        A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men.
        J Nutr. 2002; 132: 1879-1885
        • Fernandez M.L.
        • McNamara D.J.
        Regulation of cholesterol and lipoprotein metabolism in guinea pigs mediated by dietary fat quality and quantity.
        J Nutr. 1991; 121: 934-943
        • Fernandez M.L.
        • Sun D.M.
        • Tosca M.A.
        • McNamara D.J.
        Citrus pectin and cholesterol interact to regulate hepatic cholesterol homeostasis and lipoprotein metabolism: a dose–response study in guinea pigs.
        Am J Clin Nutr. 1994; 59: 869-878
        • Weber A.F.
        • Phillips M.G.
        • Bell Jr., J.T.
        An improved method for the Schultz cholesterol test.
        J Histochem Cytochem. 1956; 4: 308-309
        • Wadsworth M.P.
        • Sobel B.E.
        • Schneider D.J.
        • Taatjes D.J.
        Delineation of the evolution of compositional changes in atheroma.
        Histochem Cell Biol. 2002; 118: 59-68
        • Sharman M.J.
        • Gomez A.L.
        • Kraemer W.J.
        • Volek J.S.
        Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men.
        J Nutr. 2004; 134: 880-885
        • Torres-Gonzalez M.
        • Volek J.S.
        • Sharman M.
        • Contois J.H.
        • Fernandez M.L.
        Dietary carbohydrate and cholesterol influence the number of particles and distributions of lipoprotein subfractions in guinea pigs.
        J Nutr Biochem. 2006; 17: 773-779
        • Baranowski M.
        Biological role of liver × receptors.
        J Physiol Pharmacol. 2008; 59: 31-55
        • Leite J.O.
        • Deogburn R.
        • Ratliff J.C.
        • et al.
        Low-carbohydrate diet disrupts the association between insulin resistance and weight gain.
        Metabolism. 2009;
        • Hayek T.
        • Oiknine J.
        • Brook J.G.
        • Aviram M.
        Increased plasma and lipoprotein lipid peroxidation in apo E-deficient mice.
        Biochem Biophys Res Commun. 1994; 201: 1567-1574
        • Witztum J.L.
        • Steinberg D.
        Role of oxidized low density lipoprotein in atherogenesis.
        J Clin Invest. 1991; 88: 1785-1792
        • Bruno R.S.
        • Torres-Gonzalez M.
        • Yeung S.F.
        • et al.
        Regulation of hepatic lipids and antioxidants by dietary carbohydrate restriction and cholesterol in guinea pigs.
        FASEB J. 2008; 22: 1103.4
        • Jeanes Y.M.
        • Hall W.L.
        • Ellard S.
        • Lee E.
        • Lodge J.K.
        The absorption of vitamin E is influenced by the amount of fat in a meal and the food matrix.
        Br J Nutr. 2004; 92: 575-579
        • Torres-Gonzalez M.
        • Volek J.S.
        • Leite J.O.
        • Fraser H.
        • Fernandez M.L.
        Carbohydrate restriction reduces lipids and inflammation and prevents atherosclerosis in guinea pigs.
        J Atheroscler Thromb. 2008; 15: 235-243
        • Tararak E.M.
        Regression of experimental atherosclerosis of the aorta in guinea pigs.
        Bull Exper Biol Med. 1968; 67: 118-121
        • Rosenfeld M.E.
        • Carew T.E.
        • von Hodenberg E.
        • et al.
        Autoradiographic analysis of the distribution of 125I-tyramine-cellobiose-LDL in atherosclerotic lesions of the WHHL rabbit.
        J Arterioscler Thromb. 1992; 12: 985-995