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Dietary α-lactalbumin induced fatty liver by enhancing nuclear liver X receptor αβ/sterol regulatory element-binding protein-1c/PPARγ expression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinase α phosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice.
Br J Nutr. 2017 Dec; 118(11):914-929.BJ

Abstract

The effect and the role played by dietary α-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously that α-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 possible α-LAC-induced hepatic steatosis. We examine the ability of dietary α-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 (n 6) were fed with diets containing either chow or 14 % α-LAC for 4 weeks. The α-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 receptor αβ (LXRαβ), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγ transcription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepatic de novo lipogenesis. The opposite was found for the nuclear receptor PPARα and the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acid β-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinase α (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 the α-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/PPARγ expression and diminishing PPARα/CPT-1 expression and AMPKα phosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice.

Authors+Show Affiliations

1Sección Departamental de Fisiología, Facultad de Farmacia,Universidad Complutense de Madrid,28040 Madrid,Spain.2Departamento de Farmacología, Facultad de Farmacia,Universidad Complutense,28040 Madrid,Spain.1Sección Departamental de Fisiología, Facultad de Farmacia,Universidad Complutense de Madrid,28040 Madrid,Spain.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29173234

Citation

López-Oliva, María Elvira, et al. "Dietary Α-lactalbumin Induced Fatty Liver By Enhancing Nuclear Liver X Receptor Αβ/sterol Regulatory Element-binding protein-1c/PPARγ Expression and Minimising PPARα/carnitine Palmitoyltransferase-1 Expression and AMP-activated Protein Kinase Α Phosphorylation Associated With Atherogenic Dyslipidaemia, Insulin Resistance and Oxidative Stress in Balb/c Mice." The British Journal of Nutrition, vol. 118, no. 11, 2017, pp. 914-929.
López-Oliva ME, Garcimartin A, Muñoz-Martínez E. Dietary α-lactalbumin induced fatty liver by enhancing nuclear liver X receptor αβ/sterol regulatory element-binding protein-1c/PPARγ expression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinase α phosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice. Br J Nutr. 2017;118(11):914-929.
López-Oliva, M. E., Garcimartin, A., & Muñoz-Martínez, E. (2017). Dietary α-lactalbumin induced fatty liver by enhancing nuclear liver X receptor αβ/sterol regulatory element-binding protein-1c/PPARγ expression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinase α phosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice. The British Journal of Nutrition, 118(11), 914-929. https://doi.org/10.1017/S000711451700232X
López-Oliva ME, Garcimartin A, Muñoz-Martínez E. Dietary Α-lactalbumin Induced Fatty Liver By Enhancing Nuclear Liver X Receptor Αβ/sterol Regulatory Element-binding protein-1c/PPARγ Expression and Minimising PPARα/carnitine Palmitoyltransferase-1 Expression and AMP-activated Protein Kinase Α Phosphorylation Associated With Atherogenic Dyslipidaemia, Insulin Resistance and Oxidative Stress in Balb/c Mice. Br J Nutr. 2017;118(11):914-929. PubMed PMID: 29173234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary α-lactalbumin induced fatty liver by enhancing nuclear liver X receptor αβ/sterol regulatory element-binding protein-1c/PPARγ expression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinase α phosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice. AU - López-Oliva,María Elvira, AU - Garcimartin,Alba, AU - Muñoz-Martínez,Emilia, Y1 - 2017/11/27/ PY - 2017/11/28/pubmed PY - 2017/12/19/medline PY - 2017/11/28/entrez KW - Atherogenic dyslipidaemia KW - Dietary α-lactalbumin KW - Fatty liver KW - Oxidative stress SP - 914 EP - 929 JF - The British journal of nutrition JO - Br. J. Nutr. VL - 118 IS - 11 N2 - The effect and the role played by dietary α-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously that α-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 possible α-LAC-induced hepatic steatosis. We examine the ability of dietary α-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 (n 6) were fed with diets containing either chow or 14 % α-LAC for 4 weeks. The α-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 receptor αβ (LXRαβ), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγ transcription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepatic de novo lipogenesis. The opposite was found for the nuclear receptor PPARα and the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acid β-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinase α (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 the α-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/PPARγ expression and diminishing PPARα/CPT-1 expression and AMPKα phosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice. SN - 1475-2662 UR - https://www.unboundmedicine.com/medline/citation/29173234/Dietary_α_lactalbumin_induced_fatty_liver_by_enhancing_nuclear_liver_X_receptor_αβ/sterol_regulatory_element_binding_protein_1c/PPARγ_expression_and_minimising_PPARα/carnitine_palmitoyltransferase_1_expression_and_AMP_activated_protein_kinase_α_phosphorylation_associated_with_atherogenic_dyslipidaemia_insulin_resistance_and_oxidative_stress_in_Balb/c_mice_ L2 - https://www.cambridge.org/core/product/identifier/S000711451700232X/type/journal_article DB - PRIME DP - Unbound Medicine ER -