Author:
López-Oliva María Elvira,Garcimartin Alba,Muñoz-Martínez Emilia
Abstract
AbstractThe effect and the role played by dietaryα-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously thatα-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim of the present study was to investigate if this atherogenic effect could be due to a possibleα-LAC-induced hepatic steatosis. We examine the ability of dietaryα-LAC to induce liver steatosis, identifying the molecular mechanisms underlying hepatic lipid metabolism in association with the lipid profile, peripheral insulin resistance (IR) and changes in the hepatic oxidative environment. Male Balb/c mice (n6) were fed with diets containing either chow or 14 %α-LAC for 4 weeks. Theα-LAC-fed mice developed abdominal adiposity and IR. Moderate liver steatosis with increased TAG and NEFA contents was correlated with atherogenic dyslipidaemia. There was increased nuclear expression of liver X receptorαβ(LXRαβ), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγtranscription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepaticde novolipogenesis. The opposite was found for the nuclear receptor PPARαand the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acidβ-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinaseα(AMPKα) (inactivation) and p-Ser79-ACC1 (activation) and with a more oxidative liver environment increasing lipid peroxidation and protein oxidation and reducing GSH:GSSG ratio in theα-LAC-fed mice. In conclusion, 4 weeks of 14 %α-LAC feeding induced liver steatosis associated with atherogenic dyslipidaemia, IR and oxidative stress by enhancing nuclear LXRαβ/SREBP-1c/PPARγexpression and diminishing PPARα/CPT-1 expression and AMPKαphosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice.
Publisher
Cambridge University Press (CUP)
Subject
Nutrition and Dietetics,Medicine (miscellaneous)