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High-protein diets prevent steatosis and induce hepatic accumulation of monomethyl branched-chain fatty acids.
- Source :
-
The Journal of nutritional biochemistry [J Nutr Biochem] 2014 Dec; Vol. 25 (12), pp. 1263-74. Date of Electronic Publication: 2014 Sep 16. - Publication Year :
- 2014
-
Abstract
- The hallmark of nonalcoholic fatty liver disease is steatosis of unknown etiology. To test how dietary protein decreases steatosis, we fed female C57BL/6 J mice low-fat (8 en%) or high-fat (42 en%) combined with low-protein (11 en%), high-protein (HP; 35 en%) or extra-high-protein (HPX; 58 en%) diets for 3 weeks. The 35 en% protein diets reduced hepatic triglyceride, free fatty acid, cholesterol and phospholipid contents to ~50% of that in 11 en% protein diets. Every additional 10 en% protein reduced hepatic fat content ~1.5 g%. HP diets had no effect on lipogenic or fatty acid-oxidizing genes except Ppargc1α (+30%), increased hepatic PCK1 content 3- to 5-fold, left plasma glucose and hepatic glycogen concentration unchanged, and decreased inflammation and cell stress (decreased Fgf21 and increased Gsta expression). The HP-mediated decrease in steatosis correlated inversely with plasma branched-chain amino-acid (BCAA) concentrations and hepatic content of BCAA-derived monomethyl branched-chain fatty acids (mmBCFAs) 14-methylpentadecanoic (14-MPDA; valine-derived) and, to a lesser extent, 14-methylhexadecanoic acid (isoleucine-derived). Liver lipid content was 1.6- to 1.8-fold higher in females than in males, but the anti-steatotic effect of HP diets was equally strong. The strong up-regulation of PCK1 and literature data showing an increase in phosphoenolpyruvate and a decline in tricarboxylic acid cycle intermediates in liver reveal that an increased efflux of these intermediates from mitochondria represents an important effect of an HP diet. The HP diet-induced increase in 14-MPDA and the dietary response in gene expression were more pronounced in females than males. Our findings are compatible with a facilitating role of valine-derived mmBCFAs in the antisteatotic effect of HP diets.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Blood Glucose metabolism
Cholesterol blood
Diet, High-Fat adverse effects
Diet, Protein-Restricted
Fatty Acids, Nonesterified blood
Female
Fibroblast Growth Factors blood
Glucagon blood
Insulin blood
Leptin blood
Liver drug effects
Male
Mice
Mice, Inbred C57BL
Palmitic Acids blood
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Phospholipids blood
Sex Factors
Transcription Factors genetics
Transcription Factors metabolism
Triglycerides blood
Up-Regulation
Dietary Fats administration & dosage
Dietary Proteins administration & dosage
Fatty Liver prevention & control
Lipid Metabolism drug effects
Liver metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4847
- Volume :
- 25
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of nutritional biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 25287814
- Full Text :
- https://doi.org/10.1016/j.jnutbio.2014.07.005