Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Cholesterol-induced inflammation and macrophage accumulation in adipose tissue is reduced by a low carbohydrate diet in guinea pigs

  • Aguilar, David (Department of Nutritional Sciences, University of Connecticut) ;
  • deOgburn, Ryan C. (Department of Nutritional Sciences, University of Connecticut) ;
  • Volek, Jeff S. (Department of Nutritional Sciences, University of Connecticut) ;
  • Fernandez, Maria Luz (Department of Nutritional Sciences, University of Connecticut)
  • Received : 2014.03.10
  • Accepted : 2014.07.25
  • Published : 2014.12.01
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Abstract

BACKGROUND/OBJECTIVES: The main objective of this study was to evaluate the effects of a high cholesterol (HC) dietary challenge on cholesterol tissue accumulation, inflammation, adipocyte differentiation, and macrophage infiltration in guinea pigs. A second objective was to assess whether macronutrient manipulation would reverse these metabolic alterations. MATERIALS/METHODS: Male Hartley guinea pigs (10/group) were assigned to either low cholesterol (LC) (0.04g/100g) or high cholesterol (HC) (0.25g/100g) diets for six weeks. For the second experiment, 20 guinea pigs were fed the HC diet for six weeks and then assigned to either a low carbohydrate (CHO) diet (L-CHO) (10% energy from CHO) or a high CHO diet (H-CHO) (54% CHO) for an additional six weeks. RESULTS: Higher concentrations of total (P < 0.005) and free (P < 0.05) cholesterol were observed in both adipose tissue and aortas of guinea pigs fed the HC compared to those in the LC group. In addition, higher concentrations of pro-inflammatory cytokines in the adipose tissue (P < 0.005) and lower concentrations of anti-inflammatory interleukin (IL)-10 were observed in the HC group (P < 0.05) compared to the LC group. Of particular interest, adipocytes in the HC group were smaller in size (P < 0.05) and showed increased macrophage infiltration compared to the LC group. When compared to the H-CHO group, lower concentrations of cholesterol in both adipose and aortas as well as lower concentrations of inflammatory cytokines in adipose tissue were observed in the L-CHO group (P < 0.05). In addition, guinea pigs fed the L-CHO exhibited larger adipose cells and lower macrophage infiltration compared to the H-CHO group. CONCLUSIONS: The results of this study strongly suggest that HC induces metabolic dysregulation associated with inflammation in adipose tissue and that L-CHO is more effective than H-CHO in attenuating these detrimental effects.

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References

  1. Subramanian S, Chait A. The effect of dietary cholesterol on macrophage accumulation in adipose tissue: implications for systemic inflammation and atherosclerosis. Curr Opin Lipidol 2009;20:39-44. https://doi.org/10.1097/MOL.0b013e32831bef8b
  2. Subramanian S, Han CY, Chiba T, McMillen TS, Wang SA, Haw A 3rd, Kirk EA, O'Brien KD, Chait A. Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 2008;28:685-91. https://doi.org/10.1161/ATVBAHA.107.157685
  3. McGillicuddy FC, Reilly MP, Rader DJ. Adipose modulation of high-density lipoprotein cholesterol: implications for obesity, high-density lipoprotein metabolism, and cardiovascular disease. Circulation 2011;124:1602-5. https://doi.org/10.1161/CIRCULATIONAHA.111.058453
  4. Krause BR, Hartman AD. Adipose tissue and cholesterol metabolism. J Lipid Res 1984;25:97-110.
  5. Mari M, Caballero F, Colell A, Morales A, Caballeria J, Fernandez A, Enrich C, Fernandez-Checa JC, Garcia-Ruiz C. Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis. Cell Metab 2006;4:185-98. https://doi.org/10.1016/j.cmet.2006.07.006
  6. Schwabe RF, Maher JJ. Lipids in liver disease: looking beyond steatosis. Gastroenterology 2012;142:8-11. https://doi.org/10.1053/j.gastro.2011.11.004
  7. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444:860-7. https://doi.org/10.1038/nature05485
  8. Li H, Li H, Guo H, Liu F. Cholesterol suppresses adipocytic differentiation of mouse adipose-derived stromal cells via PPARgamma2 signaling. Steroids 2013;78:454-61. https://doi.org/10.1016/j.steroids.2013.02.009
  9. Boling CL, Westman EC, Yancy WS Jr. Carbohydrate-restricted diets for obesity and related diseases: an update. Curr Atheroscler Rep 2009;11:462-9. https://doi.org/10.1007/s11883-009-0069-8
  10. Leite JO, DeOgburn R, Ratliff J, Su R, Smyth JA, Volek JS, McGrane MM, Dardik A, Fernandez ML. Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet. Atherosclerosis 2010;209:442-8. https://doi.org/10.1016/j.atherosclerosis.2009.10.005
  11. Sharman MJ, Fernandez ML, Zern TL, Torres-Gonzalez M, Kraemer WJ, Volek JS. 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;19:732-8. https://doi.org/10.1016/j.jnutbio.2007.09.008
  12. Torres-Gonzalez M, Volek JS, Leite JO, Fraser H, Luz Fernandez M. Carbohydrate restriction reduces lipids and inflammation and prevents atherosclerosis in Guinea pigs. J Atheroscler Thromb 2008;15:235-43. https://doi.org/10.5551/jat.E5781
  13. Wylie-Rosett J, Davis NJ. Low-carbohydrate diets: an update on current research. Curr Diab Rep 2009;9:396-404. https://doi.org/10.1007/s11892-009-0061-2
  14. Kim JE, Clark RM, Park Y, Lee J, Fernandez ML. Lutein decreases oxidative stress and inflammation in liver and eyes of guinea pigs fed a hypercholesterolemic diet. Nutr Res Pract 2012;6:113-9. https://doi.org/10.4162/nrp.2012.6.2.113
  15. Carr TP, Andresen CJ, Rudel LL. Enzymatic determination of triglyceride, free cholesterol, and total cholesterol in tissue lipid extracts. Clin Biochem 1993;26:39-42. https://doi.org/10.1016/0009-9120(93)90015-X
  16. Kim JE, Leite JO, DeOgburn R, Smyth JA, Clark RM, Fernandez ML. A lutein-enriched diet prevents cholesterol accumulation and decreases oxidized LDL and inflammatory cytokines in the aorta of guinea pigs. J Nutr 2011;141:1458-63. https://doi.org/10.3945/jn.111.141630
  17. Torres-Gonzalez M, Shrestha S, Sharman M, Freake HC, Volek JS, Fernandez ML. Carbohydrate restriction alters hepatic cholesterol metabolism in guinea pigs fed a hypercholesterolemic diet. J Nutr 2007;137:2219-23.
  18. Volek JS, Fernandez ML, Feinman RD, Phinney SD. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog Lipid Res 2008;47:307-18. https://doi.org/10.1016/j.plipres.2008.02.003
  19. Rackova L. Cholesterol load of microglia: contribution of membrane architecture changes to neurotoxic power? Arch Biochem Biophys 2013;537:91-103. https://doi.org/10.1016/j.abb.2013.06.015
  20. Terrand J, Bruban V, Zhou L, Gong W, El Asmar Z, May P, Zurhove K, Haffner P, Philippe C, Woldt E, Matz RL, Gracia C, Metzger D, Auwerx J, Herz J, Boucher P. LRP1 controls intracellular cholesterol storage and fatty acid synthesis through modulation of Wnt signaling. J Biol Chem 2009;284:381-8. https://doi.org/10.1074/jbc.M806538200
  21. Hofmann SM, Zhou L, Perez-Tilve D, Greer T, Grant E, Wancata L, Thomas A, Pfluger PT, Basford JE, Gilham D, Herz J, Tschop MH, Hui DY. Adipocyte LDL receptor-related protein-1 expression modulates postprandial lipid transport and glucose homeostasis in mice. J Clin Invest 2007;117:3271-82. https://doi.org/10.1172/JCI31929
  22. Shimano H, Horton JD, Hammer RE, Shimomura I, Brown MS, Goldstein JL. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J Clin Invest 1996;98:1575-84. https://doi.org/10.1172/JCI118951
  23. Lowell BB. PPARgamma: an essential regulator of adipogenesis and modulator of fat cell function. Cell 1999;99:239-42. https://doi.org/10.1016/S0092-8674(00)81654-2
  24. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994;79:1147-56. https://doi.org/10.1016/0092-8674(94)90006-X
  25. Shimomura I, Bashmakov Y, Shimano H, Horton JD, Goldstein JL, Brown MS. Cholesterol feeding reduces nuclear forms of sterol regulatory element binding proteins in hamster liver. Proc Natl Acad Sci U S A 1997;94:12354-9. https://doi.org/10.1073/pnas.94.23.12354
  26. Cucuianu M, Coca M, Hancu N. Reverse cholesterol transport and atherosclerosis. A mini review. Rom J Intern Med 2007;45:17-27.
  27. Zhang Y, McGillicuddy FC, Hinkle CC, O'Neill S, Glick JM, Rothblat GH, Reilly MP. Adipocyte modulation of high-density lipoprotein cholesterol. Circulation 2010;121:1347-55. https://doi.org/10.1161/CIRCULATIONAHA.109.897330
  28. Chung S, Sawyer JK, Gebre AK, Maeda N, Parks JS. Adipose tissue ATP binding cassette transporter A1 contributes to high-density lipoprotein biogenesis in vivo. Circulation 2011;124:1663-72. https://doi.org/10.1161/CIRCULATIONAHA.111.025445
  29. Aronson D, Rayfield EJ. How hyperglycemia promotes atherosclerosis: molecular mechanisms. Cardiovasc Diabetol 2002;1:1. https://doi.org/10.1186/1475-2840-1-1
  30. Bucala R, Makita Z, Koschinsky T, Cerami A, Vlassara H. Lipid advanced glycosylation: pathway for lipid oxidation in vivo. Proc Natl Acad Sci U S A 1993;90:6434-8. https://doi.org/10.1073/pnas.90.14.6434
  31. Bucala R, Makita Z, Vega G, Grundy S, Koschinsky T, Cerami A, Vlassara H. Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency. Proc Natl Acad Sci U S A 1994;91:9441-5. https://doi.org/10.1073/pnas.91.20.9441
  32. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988;318:1315-21. https://doi.org/10.1056/NEJM198805193182007
  33. Baranowski M. Biological role of liver X receptors. J Physiol Pharmacol 2008;59 Suppl 7:31-55.
  34. Leite JO, DeOgburn R, Ratliff JC, Su R, Volek JS, McGrane MM, Dardik A, Fernandez ML. Low-carbohydrate diet disrupts the association between insulin resistance and weight gain. Metabolism 2009;58:1116-22. https://doi.org/10.1016/j.metabol.2009.04.004

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