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

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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

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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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