Characterisation of atherogenic effects of low carbohydrate, high protein diet (LCHP) in apoE/LDLR−/− mice

INTRODUCTION: Low Carbohydrate High Protein diet represents a popular strategy to achieve weight loss. OBJECTIVE: The aim of this study was to characterize effects of low carbohydrate, high protein diet (LCHP) on atherosclerotic plaque development in brachiocephalic artery (BCA) in apoE/LDLR⁻/⁻ mice...

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Published in:The Journal of nutrition, health & aging health & aging, 2015-08, Vol.19 (7), p.710-718
Main Authors: Kostogrys, Renata B, Johann, C, Czyżyńska, I, Franczyk-Żarów, M, Drahun, A, Maślak, E, Jasztal, A, Gajda, M, Mateuszuk, Ł, Wrobel, T. P, Baranska, M, Wybrańska, I, Jezkova, K, Nachtigal, P, Chlopicki, S
Format: Article
Language:English
Subjects:
Acute-Phase Reaction - chemically induced
Aging
Animals
aorta
Aorta - drug effects
Aorta - pathology
Apolipoproteins E - deficiency
Apolipoproteins E - genetics
atherosclerosis
Atherosclerosis - blood
Atherosclerosis - chemically induced
biomarkers
Brachiocephalic Trunk - drug effects
Brachiocephalic Trunk - pathology
cholesterol
Cholesterol, LDL - blood
Cholesterol, VLDL - blood
Diet, Atherogenic - adverse effects
Diet, Carbohydrate-Restricted - adverse effects
Dietary Proteins - administration & dosage
Dietary Proteins - pharmacology
Female
Fourier transform infrared spectroscopy
Geriatrics/Gerontology
haptoglobins
high protein diet
inflammation
Inflammation - chemically induced
liver
Liver - drug effects
Liver - metabolism
low density lipoprotein
macrophages
Macrophages - drug effects
Male
Medicine
Medicine & Public Health
Mice
Mice, Knockout
mortality
Neurosciences
Nutrition
phenotype
Plaque, Atherosclerotic - blood
Plaque, Atherosclerotic - chemically induced
Primary Care Medicine
Quality of Life Research
Receptors, LDL - deficiency
Receptors, LDL - genetics
Sterol Regulatory Element Binding Protein 1 - metabolism
Survival Analysis
transcription factors
Triglycerides - blood
urea
Urea - blood
very low density lipoprotein
weight loss
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Summary:INTRODUCTION: Low Carbohydrate High Protein diet represents a popular strategy to achieve weight loss. OBJECTIVE: The aim of this study was to characterize effects of low carbohydrate, high protein diet (LCHP) on atherosclerotic plaque development in brachiocephalic artery (BCA) in apoE/LDLR⁻/⁻ mice and to elucidate mechanisms of proatherogenic effects of LCHP diet. MATERIALS AND METHODS: Atherosclerosis plaques in brachiocephalic artery (BCA) as well as in aortic roots, lipoprotein profile, inflammation biomarkers, expression of SREBP-1 in the liver as well as mortality were analyzed in Control diet (AIN-93G) or LCHP (Low Carbohydrate High Protein) diet fed mice. RESULTS: Area of atherosclerotic plaques in aortic roots or BCA from LCHP diet fed mice was substantially increased as compared to mice fed control diet and was characterized by increased lipids and cholesterol contents (ORO staining, FT-IR analysis), increased macrophage infiltration (MOMA-2) and activity of MMPs (zymography). Pro-atherogenic phenotype of LCHP fed apoE/LDLR⁻/⁻ mice was associated with increased plasma total cholesterol concentration, and in LDL and VLDL fractions, increased TG contents in VLDL, and a modest increase in plasma urea. LCHP diet increased SCD-1 index, activated SREBP-1 transcription factor in the liver and triggered acute phase response as evidence by an increased plasma concentration of haptoglobin, CRP or AGP. Finally, in long-term experiment survival of apoE/LDLR⁻/⁻ mice fed LCHP diet was substantially reduced as compared to their counterparts fed control diet suggesting overall detrimental effects of LCHP diet on health. CONCLUSIONS: The pro-atherogenic effect of LCHP diet in apoE/LDLR⁻/⁻ mice is associated with profound increase in LDL and VLDL cholesterol, VLDL triglicerides, liver SREBP-1 upregulation, and systemic inflammation.
ISSN:1279-7707
1760-4788
DOI:10.1007/s12603-015-0543-7