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http://dx.doi.org/10.4162/nrp.2014.8.6.625

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)
Publication Information
Nutrition Research and Practice / v.8, no.6, 2014 , pp. 625-631 More about this Journal
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.
Keywords
Adipose; inflammation; dietary cholesterol; high carbohydrate; guinea pigs;
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1 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.   DOI   ScienceOn
2 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.   DOI   ScienceOn
3 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.   DOI   ScienceOn
4 Wylie-Rosett J, Davis NJ. Low-carbohydrate diets: an update on current research. Curr Diab Rep 2009;9:396-404.   DOI   ScienceOn
5 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.   DOI   ScienceOn
6 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.   DOI   ScienceOn
7 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.   DOI   ScienceOn
8 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.
9 Rackova L. Cholesterol load of microglia: contribution of membrane architecture changes to neurotoxic power? Arch Biochem Biophys 2013;537:91-103.   DOI   ScienceOn
10 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.   DOI   ScienceOn
11 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.   DOI   ScienceOn
12 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.   DOI   ScienceOn
13 Cucuianu M, Coca M, Hancu N. Reverse cholesterol transport and atherosclerosis. A mini review. Rom J Intern Med 2007;45:17-27.
14 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.   DOI   ScienceOn
15 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.   DOI
16 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.   DOI   ScienceOn
17 Baranowski M. Biological role of liver X receptors. J Physiol Pharmacol 2008;59 Suppl 7:31-55.
18 Aronson D, Rayfield EJ. How hyperglycemia promotes atherosclerosis: molecular mechanisms. Cardiovasc Diabetol 2002;1:1.   DOI
19 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.   DOI   ScienceOn
20 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.   DOI   ScienceOn
21 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.   DOI   ScienceOn
22 Krause BR, Hartman AD. Adipose tissue and cholesterol metabolism. J Lipid Res 1984;25:97-110.
23 Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444:860-7.   DOI   ScienceOn
24 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.   DOI   ScienceOn
25 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.   DOI   ScienceOn
26 Schwabe RF, Maher JJ. Lipids in liver disease: looking beyond steatosis. Gastroenterology 2012;142:8-11.   DOI   ScienceOn
27 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.   DOI   ScienceOn
28 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.   DOI   ScienceOn
29 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.   DOI   ScienceOn
30 Boling CL, Westman EC, Yancy WS Jr. Carbohydrate-restricted diets for obesity and related diseases: an update. Curr Atheroscler Rep 2009;11:462-9.   DOI
31 Lowell BB. PPARgamma: an essential regulator of adipogenesis and modulator of fat cell function. Cell 1999;99:239-42.   DOI   ScienceOn
32 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.   DOI   ScienceOn
33 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.   DOI   ScienceOn
34 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.   DOI   ScienceOn