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Fish Oil Normalizes Plasma Glucose Levels and Improves Liver Carbohydrate Metabolism in Rats Fed a Sucrose-Rich Diet

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Lipids

Abstract

A sucrose-rich diet (SRD) induces insulin resistance and dyslipidemia with impaired hepatic glucose production and gluconeogenesis, accompanied by altered post-receptor insulin signaling steps. The aim of this study was to examine the effectiveness of fish oil (FO) to reverse or improve the impaired hepatic glucose metabolism once installed in rats fed 8 months a SRD. In the liver of rats fed SRD in which FO replaced corn-oil during the last 2 months, as dietary fat, several key enzyme activities and metabolites involved in glucose metabolisms (phosphorylation, glycolysis, gluconeogenesis and oxidative and non oxidative glucose pathway) were measured. The protein mass levels of IRS-1 and αp85 PI-3K at basal conditions were also analyzed. FO improved the altered activities of some enzymes involved in the glycolytic and oxidative pathways observed in the liver of SRD fed rats but was unable to restore the impaired capacity of glucose phosphorylation. Moreover, FO reversed the increase in PEPCK and G-6-Pase and reduced the G-6-Pase/GK ratio. Glycogen concentration and GSa activity returned to levels similar to those observed in the liver of the control-fed rats. Besides, FO did not modify the altered protein mass levels of IRS-1 and αp85 PI-3K. Finally, dietary FO was effective in reversing or improving the impaired activities of several key enzymes of hepatic carbohydrate metabolism contributing, at least in part, to the normalization of plasma glucose levels in the SRD-fed rats. However, these positive effects of FO were not observed under basal conditions in the early steps of insulin signaling transduction.

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Abbreviations

AKt:

Serine/threonine protein kinase

AMPKα2:

AMP activated kinase isoform

C:

Cholesterol

CD:

High starch diet

ChREBP:

Carbohydrate response element binding protein

CO:

Corn oil

DAGT:

Diacylglycerol acyltransferase

FFA:

Unesterified fatty acids

FO:

Fish oil

G-6-Pase:

Glucose-6-phosphate phosphatase

GK:

Glucokinase

Glucose-6-P:

Glucose-6-phosphate

Glut2 and Glut4:

Glucose transporters 2 and 4

GSa:

Glycogen synthase a

HK:

Hexokinase

IRS:

Insulin receptor substrate

JNK:

c-jun N terminal kinase

LXR:

Liver X receptor

PDHa:

Pyruvate dehydrogenase active form

PDHc:

PDH complex

PEPCK:

Phosphoenolpyruvate carboxykinase

PI-3K:

Phosphoinositide-3 kinase

PK:

Pyruvate kinase

PPARα:

Peroxisome proliferators activated receptor α

PUFA:

Polyunsaturated fatty acid(s)

SRD:

Sucrose rich diet

TAG:

Triacylglycerol(s)

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Acknowledgments

This study was supported by Grants PICT 05-38157 BID 1728 OC/AR and PIP # 11220090100105, 2010 from the Agencia Nacional de Promoción Científica y Tecnológica and CONICET.

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Authors and Affiliations

  1. Department of Biochemistry, School of Biochemistry, University of Litoral, Ciudad Universitaria Paraje El Pozo. CC 242 (3000), Santa Fe, Argentina

    Gustavo J. Hein, Adriana Chicco & Yolanda B. Lombardo

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  1. Gustavo J. Hein
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  2. Adriana Chicco
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  3. Yolanda B. Lombardo
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Correspondence to Yolanda B. Lombardo.

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Hein, G.J., Chicco, A. & Lombardo, Y.B. Fish Oil Normalizes Plasma Glucose Levels and Improves Liver Carbohydrate Metabolism in Rats Fed a Sucrose-Rich Diet. Lipids 47, 141–150 (2012). https://doi.org/10.1007/s11745-011-3623-4

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