Supplementation with an insoluble fiber obtained from carob pod (Ceratonia siliqua L.) rich in polyphenols prevents dyslipidemia in rabbits through SIRT1/PGC-1α pathway

Abstract

Purpose

To investigate the mechanism implicated in the effect of an insoluble fiber (obtained from carob pod) rich in polyphenols (IFCP) in lipid metabolism in the liver.

Methods

Male New Zealand rabbits were fed with the following diets for 8 weeks: control diet (CT group), dyslipidemic diet supplemented with 0.5% cholesterol + 14% coconut oil (DL group) and dyslipidemic diet containing 0.5% cholesterol + 14% coconut oil plus 3% IFCP (DL + IFCP group).

Results

Dyslipidemic diet with IFCP was able to reduce development of mixed dyslipidemia, liver relative weight and collagen I protein expression compared to DL rabbits. Analyses of the main enzymes implicated in cholesterol and triglycerides metabolism revealed that IFCP increased hepatic concentration of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and cytochrome P450, family 7, subfamily a, polypeptide 1C (CYP7A1) (82.34, 114.42%, respectively) as well as protein expression of LDL receptor (42.48%) in DL rabbits. Importantly, IFCP also increased hepatic lipase (HL) levels (91.43%) and decreased glycerol phosphate acyltransferase (GPAT) and sterol regulatory element-binding protein 1C (SREBP1c) liver expression levels (20.38 and 41.20%, respectively). Finally, sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) hepatic expression increased in DL + IFCP group compared with DL (159.81 and 48.00%, respectively).

Conclusions

These findings show that IFCP is able to abrogate the deleterious effects of hepatic dyslipidemia by modulating SIRT1 and PGC-1α pathways.

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Abbreviations

CYP7A1:

Cytochrome P450, family 7, subfamily a, polypeptide 1C

FXR:

Farnesoid x receptor

GPAT:

Glycerol phosphate acyltransferase

HL:

Hepatic lipase

HMG-CoA reductase:

3-Hydroxy-3-methylglutaryl-CoA reductase

LDLR:

LDL receptor

LXR:

Liver x receptor

PGC-1α:

Peroxisome proliferator-activated receptor gamma coactivator-1alpha

PPAR:

Peroxisome proliferator-activated receptor

SIRT1:

Sirtuin1

SREBP-1C:

Sterol regulatory element-binding protein 1C

References

  1. 1.

    Vazzana N, Santilli F, Sestili S, Cuccurullo C, Davi G (2011) Determinants of increased cardiovascular disease in obesity and metabolic syndrome. Curr Med Chem 18(34):5267–5280

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    Recinos A 3rd, Carr BK, Bartos DB, Boldogh I, Carmical JR, Belalcazar LM, Brasier AR (2004) Liver gene expression associated with diet and lesion development in atherosclerosis-prone mice: induction of components of alternative complement pathway. Physiol Genom 19(1):131–142. https://doi.org/10.1152/physiolgenomics.00146.2003

    Article  CAS  Google Scholar 

  3. 3.

    Moore KJ, Rayner KJ, Suarez Y, Fernandez-Hernando C (2010) microRNAs and cholesterol metabolism. Trends Endocrinol Metab 21(12):699–706. https://doi.org/10.1016/j.tem.2010.08.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Anderson N, Borlak J (2008) Molecular mechanisms and therapeutic targets in steatosis and steatohepatitis. Pharmacol Rev 60(3):311–357. https://doi.org/10.1124/pr.108.00001

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Panda T, Devi VA (2004) Regulation and degradation of HMGCo-A reductase. Appl Microbiol Biotechnol 66(2):143–152. https://doi.org/10.1007/s00253-004-1720-5

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    DeBose-Boyd RA (2008) Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase. Cell Res 18(6):609–621. https://doi.org/10.1038/cr.2008.61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Zou Y, Du H, Yin M, Zhang L, Mao L, Xiao N, Ren G, Zhang C, Pan J (2009) Effects of high dietary fat and cholesterol on expression of PPAR alpha, LXR alpha, and their responsive genes in the liver of apoE and LDLR double deficient mice. Mol Cell Biochem 323(1–2):195–205. https://doi.org/10.1007/s11010-008-9982-3

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Kim EJ, Kim E, Kwon EY, Jang HS, Hur CG, Choi MS (2010) Network analysis of hepatic genes responded to high-fat diet in C57BL/6J mice: nutrigenomics data mining from recent research findings. J Med Food 13(4):743–756. https://doi.org/10.1089/jmf.2009.1350

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Redinger RN (2003) Nuclear receptors in cholesterol catabolism: molecular biology of the enterohepatic circulation of bile salts and its role in cholesterol homeostasis. J Lab Clin Med 142(1):7–20. https://doi.org/10.1016/S0022-2143(03)00088-X

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Caiozzi G, Wong BS, Ricketts ML (2012) Dietary modification of metabolic pathways via nuclear hormone receptors. Cell Biochem Funct 30(7):531–551. https://doi.org/10.1002/cbf.2842

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Zschoernig B, Mahlknecht U (2008) SIRTUIN 1: regulating the regulator. Biochem Biophys Res Commun 376(2):251–255. https://doi.org/10.1016/j.bbrc.2008.08.137

    Article  CAS  PubMed  Google Scholar 

  12. 12.

    Schug TT, Li X (2011) Sirtuin 1 in lipid metabolism and obesity. Ann Med 43(3):198–211. https://doi.org/10.3109/07853890.2010.547211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P (2008) Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett 582(1):46–53. https://doi.org/10.1016/j.febslet.2007.11.034

    Article  CAS  PubMed  Google Scholar 

  14. 14.

    Dominy JE Jr, Lee Y, Gerhart-Hines Z, Puigserver P (2010) Nutrient-dependent regulation of PGC-1alpha’s acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5. Biochim Biophys Acta 1804(8):1676–1683. https://doi.org/10.1016/j.bbapap.2009.11.023

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413(6852):131–138. https://doi.org/10.1038/35093050

    Article  CAS  Google Scholar 

  16. 16.

    Gu C, Zeng Y, Tang Z, Wang C, He Y, Feng X, Zhou L (2015) Astragalus polysaccharides affect insulin resistance by regulating the hepatic SIRT1-PGC-1alpha/PPARalpha-FGF21 signaling pathway in male Sprague Dawley rats undergoing catch-up growth. Mol Med Rep 12(5):6451–6460. https://doi.org/10.3892/mmr.2015.4245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Lieber CS, Leo MA, Wang X, Decarli LM (2008) Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1alpha in rats. Biochem Biophys Res Commun 370(1):44–48. https://doi.org/10.1016/j.bbrc.2008.03.005

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    You M, Liang X, Ajmo JM, Ness GC (2008) Involvement of mammalian sirtuin 1 in the action of ethanol in the liver. Am J Physiol Gastrointest Liver Physiol 294(4):G892–G898. https://doi.org/10.1152/ajpgi.00575.2007

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Howard BV, Van Horn L, Hsia J, Manson JE, Stefanick ML, Wassertheil-Smoller S, Kuller LH, LaCroix AZ, Langer RD, Lasser NL, Lewis CE, Limacher MC, Margolis KL, Mysiw WJ, Ockene JK, Parker LM, Perri MG, Phillips L, Prentice RL, Robbins J, Rossouw JE, Sarto GE, Schatz IJ, Snetselaar LG, Stevens VJ, Tinker LF, Trevisan M, Vitolins MZ, Anderson GL, Assaf AR, Bassford T, Beresford SA, Black HR, Brunner RL, Brzyski RG, Caan B, Chlebowski RT, Gass M, Granek I, Greenland P, Hays J, Heber D, Heiss G, Hendrix SL, Hubbell FA, Johnson KC, Kotchen JM (2006) Low-fat dietary pattern and risk of cardiovascular disease: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295(6):655–666. https://doi.org/10.1001/jama.295.6.655

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Papanikolaou Y, Fulgoni VL 3rd (2008) Bean consumption is associated with greater nutrient intake, reduced systolic blood pressure, lower body weight, and a smaller waist circumference in adults: results from the National Health and Nutrition Examination Survey 1999–2002. J Am Coll Nutr 27(5):569–576

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, Gomez-Gracia E, Ruiz-Gutierrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pinto X, Basora J, Munoz MA, Sorli JV, Martinez JA, Martinez-Gonzalez MA, Investigators PS (2013) Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 368(14):1279–1290. https://doi.org/10.1056/NEJMoa1200303

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Wursch P (1979) Influence of tannin-rich carob pod fiber on the cholesterol metabolism in the rat. J Nutr 109(4):685–692

    Article  CAS  PubMed  Google Scholar 

  23. 23.

    Zunft HJ, Luder W, Harde A, Haber B, Graubaum HJ, Koebnick C, Grunwald J (2003) Carob pulp preparation rich in insoluble fibre lowers total and LDL cholesterol in hypercholesterolemic patients. Eur J Nutr 42(5):235–242. https://doi.org/10.1007/s00394-003-0438-y

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Ruiz-Roso B, Quintela JC, de la Fuente E, Haya J, Perez-Olleros L (2010) Insoluble carob fiber rich in polyphenols lowers total and LDL cholesterol in hypercholesterolemic sujects. Plant Foods Hum Nutr 65(1):50–56. https://doi.org/10.1007/s11130-009-0153-9

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Proenca LM, Mayer J (2014) Prescription diets for rabbits. Vet Clin N Am Exot Anim Pract 17(3):485–502. https://doi.org/10.1016/j.cvex.2014.05.009

    Article  Google Scholar 

  26. 26.

    Papagiannopoulos M, Wollseifen HR, Mellenthin A, Haber B, Galensa R (2004) Identification and quantification of polyphenols in carob fruits (Ceratonia siliqua L.) and derived products by HPLC-UV-ESI/MSn. J Agric Food Chem 52(12):3784–3791. https://doi.org/10.1021/jf030660y

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Bastida S, Sanchez-Muniz FJ, Olivero R, Perez-Olleros L, Ruiz-Roso B, Jimenez-Colmenero F (2009) Antioxidant activity of Carob fruit extracts in cooked pork meat systems during chilled and frozen storage. Food Chem 116(3):748–754. https://doi.org/10.1016/j.foodchem.2009.03.034

    Article  CAS  Google Scholar 

  28. 28.

    Russo MA, Sansone L, Polletta L, Runci A, Rashid MM, De Santis E, Vernucci E, Carnevale I, Tafani M (2014) Sirtuins and resveratrol-derived compounds: a model for understanding the beneficial effects of the Mediterranean diet. Endocr Metab Immune Disord Drug Targets 14(4):300–308

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    Eo H, Jeon YJ, Lee M, Lim Y (2015) Brown Alga Ecklonia cava polyphenol extract ameliorates hepatic lipogenesis, oxidative stress, and inflammation by activation of AMPK and SIRT1 in high-fat diet-induced obese mice. J Agric Food Chem 63(1):349–359. https://doi.org/10.1021/jf502830b

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    Ruiz-Roso B, Quintela JC, de la Fuente E, Haya J, Perez-Olleros L (2010) Insoluble carob fiber rich in polyphenols lowers total and LDL cholesterol in hypercholesterolemic subjects. Plant Food Hum Nutr 65(1):50–56. https://doi.org/10.1007/s11130-009-0153-9

    Article  CAS  Google Scholar 

  31. 31.

    Gomez-Hernandez A, Otero YF, de las Heras N, Escribano O, Cachofeiro V, Lahera V, Benito M (2012) Brown fat lipoatrophy and increased visceral adiposity through a concerted adipocytokines overexpression induces vascular insulin resistance and dysfunction. Endocrinology 153(3):1242–1255. https://doi.org/10.1210/en.2011-1765

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    Valero-Munoz M, Martin-Fernandez B, Ballesteros S, Martinez-Martinez E, Blanco-Rivero J, Balfagon G, Cachofeiro V, Lahera V, de las Heras N (2013) Relevance of vascular peroxisome proliferator-activated receptor gamma coactivator-1alpha to molecular alterations in atherosclerosis. Exp Physiol 98(5):999–1008. https://doi.org/10.1113/expphysiol.2012.070557

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Teodoro JS, Rolo AP, Palmeira CM (2011) Hepatic FXR: key regulator of whole-body energy metabolism. Trends Endocrinol Metab 22(11):458–466. https://doi.org/10.1016/j.tem.2011.07.002

    Article  CAS  Google Scholar 

  34. 34.

    Cote I, Ngo Sock ET, Levy E, Lavoie JM (2013) An atherogenic diet decreases liver FXR gene expression and causes severe hepatic steatosis and hepatic cholesterol accumulation: effect of endurance training. Eur J Nutr 52(5):1523–1532. https://doi.org/10.1007/s00394-012-0459-5

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Rodgers JT, Puigserver P (2007) Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. Proc Natl Acad Sci USA 104(31):12861–12866. https://doi.org/10.1073/pnas.0702509104

    Article  CAS  PubMed  Google Scholar 

  36. 36.

    Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X (2009) Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab 9(4):327–338. https://doi.org/10.1016/j.cmet.2009.02.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Rhee J, Ge H, Yang W, Fan M, Handschin C, Cooper M, Lin J, Li C, Spiegelman BM (2006) Partnership of PGC-1alpha and HNF4alpha in the regulation of lipoprotein metabolism. J Biol Chem 281(21):14683–14690. https://doi.org/10.1074/jbc.M512636200

    Article  CAS  PubMed  Google Scholar 

  38. 38.

    Weber TE, Trabue SL, Ziemer CJ, Kerr BJ (2010) Evaluation of elevated dietary corn fiber from corn germ meal in growing female pigs. J Anim Sci 88(1):192–201. https://doi.org/10.2527/jas.2009-1896

    Article  CAS  PubMed  Google Scholar 

  39. 39.

    You M, Cao Q, Liang X, Ajmo JM, Ness GC (2008) Mammalian sirtuin 1 is involved in the protective action of dietary saturated fat against alcoholic fatty liver in mice. J Nutr 138(3):497–501

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Ponugoti B, Kim DH, Xiao Z, Smith Z, Miao J, Zang M, Wu SY, Chiang CM, Veenstra TD, Kemper JK (2010) SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. J Biol Chem 285(44):33959–33970. https://doi.org/10.1074/jbc.M110.122978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Wang S, Moustaid-Moussa N, Chen L, Mo H, Shastri A, Su R, Bapat P, Kwun I, Shen CL (2014) Novel insights of dietary polyphenols and obesity. J Nutr Biochem 25(1):1–18. https://doi.org/10.1016/j.jnutbio.2013.09.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Lomb DJ, Laurent G, Haigis MC (2010) Sirtuins regulate key aspects of lipid metabolism. Biochim Biophys Acta 1804(8):1652–1657. https://doi.org/10.1016/j.bbapap.2009.11.021

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    Shimano H (2009) SREBPs: physiology and pathophysiology of the SREBP family. FEBS J 276(3):616–621. https://doi.org/10.1111/j.1742-4658.2008.06806.x

    Article  CAS  PubMed  Google Scholar 

  44. 44.

    Ferre P, Foufelle F (2007) SREBP-1c transcription factor and lipid homeostasis: clinical perspective. Horm Res 68(2):72–82. https://doi.org/10.1159/000100426

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Wang Y, Viscarra J, Kim SJ, Sul HS (2015) Transcriptional regulation of hepatic lipogenesis. Nat Rev Mol Cell Biol 16(11):678–689. https://doi.org/10.1038/nrm4074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Ejaz A, Wu D, Kwan P, Meydani M (2009) Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr 139(5):919–925. https://doi.org/10.3945/jn.108.100966

    Article  CAS  PubMed  Google Scholar 

  47. 47.

    Rhee J, Inoue Y, Yoon JC, Puigserver P, Fan M, Gonzalez FJ, Spiegelman BM (2003) Regulation of hepatic fasting response by PPARgamma coactivator-1alpha (PGC-1): requirement for hepatocyte nuclear factor 4alpha in gluconeogenesis. Proc Natl Acad Sci USA 100(7):4012–4017. https://doi.org/10.1073/pnas.0730870100

    Article  CAS  PubMed  Google Scholar 

  48. 48.

    Shin DJ, Campos JA, Gil G, Osborne TF (2003) PGC-1alpha activates CYP7A1 and bile acid biosynthesis. J Biol Chem 278(50):50047–50052. https://doi.org/10.1074/jbc.M309736200

    Article  CAS  PubMed  Google Scholar 

  49. 49.

    Li X, Lian F, Liu C, Hu KQ, Wang XD (2015) Isocaloric pair-fed high-carbohydrate diet induced more hepatic steatosis and inflammation than high-fat diet mediated by miR-34a/SIRT1 axis in mice. Sci Rep 5:16774. https://doi.org/10.1038/srep16774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Kazgan N, Metukuri MR, Purushotham A, Lu J, Rao A, Lee S, Pratt-Hyatt M, Lickteig A, Csanaky IL, Zhao Y, Dawson PA, Li X (2014) Intestine-specific deletion of SIRT1 in mice impairs DCoH2-HNF-1alpha-FXR signaling and alters systemic bile acid homeostasis. Gastroenterology 146(4):1006–1016. https://doi.org/10.1053/j.gastro.2013.12.029

    Article  CAS  PubMed  Google Scholar 

  51. 51.

    Liaset B, Hao Q, Jorgensen H, Hallenborg P, Du ZY, Ma T, Marschall HU, Kruhoffer M, Li R, Li Q, Yde CC, Criales G, Bertram HC, Mellgren G, Ofjord ES, Lock EJ, Espe M, Froyland L, Madsen L, Kristiansen K (2011) Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome. J Biol Chem 286(32):28382–28395. https://doi.org/10.1074/jbc.M111.234732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Henkel AS, Anderson KA, Dewey AM, Kavesh MH, Green RM (2011) A chronic high-cholesterol diet paradoxically suppresses hepatic CYP7A1 expression in FVB/NJ mice. J Lipid Res 52(2):289–298. https://doi.org/10.1194/jlr.M012781

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Fukushima M, Nakano M, Morii Y, Ohashi T, Fujiwara Y, Sonoyama K (2000) Hepatic LDL receptor mRNA in rats is increased by dietary mushroom (Agaricus bisporus) fiber and sugar beet fiber. J Nutr 130(9):2151–2156

    Article  CAS  PubMed  Google Scholar 

  54. 54.

    Fukushima M, Ohashi T, Fujiwara Y, Sonoyama K, Nakano M (2001) Cholesterol-lowering effects of maitake (Grifola frondosa) fiber, shiitake (Lentinus edodes) fiber, and enokitake (Flammulina velutipes) fiber in rats. Exp Biol Med (Maywood) 226(8):758–765

    Article  CAS  Google Scholar 

  55. 55.

    Ramjiganesh T, Roy S, Freake HC, McIntyre JC, Fernandez ML (2002) Corn fiber oil lowers plasma cholesterol by altering hepatic cholesterol metabolism and up-regulating LDL receptors in guinea pigs. J Nutr 132(3):335–340

    Article  CAS  PubMed  Google Scholar 

  56. 56.

    Shibata S, Hayakawa K, Egashira Y, Sanada H (2007) Roles of nuclear receptors in the up-regulation of hepatic cholesterol 7alpha-hydroxylase by cholestyramine in rats. Life Sci 80(6):546–553. https://doi.org/10.1016/j.lfs.2006.10.003

    Article  CAS  PubMed  Google Scholar 

  57. 57.

    Saura-Calixto F, Perez-Jimenez J, Tourino S, Serrano J, Fuguet E, Torres JL, Goni I (2010) Proanthocyanidin metabolites associated with dietary fibre from in vitro colonic fermentation and proanthocyanidin metabolites in human plasma. Mol Nutr Food Res 54(7):939–946. https://doi.org/10.1002/mnfr.200900276

    Article  CAS  PubMed  Google Scholar 

  58. 58.

    Owen RW, Haubner R, Hull WE, Erben G, Spiegelhalder B, Bartsch H, Haber B (2003) Isolation and structure elucidation of the major individual polyphenols in carob fibre. Food Chem Toxicol 41(12):1727–1738

    Article  CAS  Google Scholar 

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Funding

This work was supported by grants from Comisión Interministerial de Ciencia y Tecnología de España [SAF2011-30396] and Ministerio de Ciencia e Innovación [IPT-2012-0213-060000].

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MV-M: conceived and designed the experiments; performed the experiments; analyzed the data; wrote the paper. SB: performed the experiments; analyzed the data. BRR: conceived and designed the experiments; analyzed the data and wrote the materials and methods. LP-O: conceived and designed the experiments; analyzed the data. BM-F: conceived and designed the experiments; analyzed the data. VL: conceived and designed the experiments; analyzed the data; wrote the paper. NH: conceived and designed the experiments; performed the experiments; analyzed the data; wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Natalia de las Heras.

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Valero-Muñoz, M., Ballesteros, S., Ruiz-Roso, B. et al. Supplementation with an insoluble fiber obtained from carob pod (Ceratonia siliqua L.) rich in polyphenols prevents dyslipidemia in rabbits through SIRT1/PGC-1α pathway. Eur J Nutr 58, 357–366 (2019). https://doi.org/10.1007/s00394-017-1599-4

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Keywords

  • Insoluble fiber from carob pod
  • Polyphenols
  • Dyslipidemia
  • SIRT1
  • PGC-1α