title: Consequences of exchanging carbohydrates for proteins in the cholesterol metabolism of mice fed a high-fat diet.
abstract: Consumption of low-carbohydrate, high-protein, high-fat diets lead to rapid weight loss but the cardioprotective effects of these diets have been questioned. We examined the impact of high-protein and high-fat diets on cholesterol metabolism by comparing the plasma cholesterol and the expression of cholesterol biosynthesis genes in the liver of mice fed a high-fat (HF) diet that has a high (H) or a low (L) protein-to-carbohydrate (P/C) ratio. H-P/C-HF feeding, compared with L-P/C-HF feeding, decreased plasma total cholesterol and increased HDL cholesterol concentrations at 4-wk. Interestingly, the expression of genes involved in hepatic steroid biosynthesis responded to an increased dietary P/C ratio by first down-regulation (2-d) followed by later up-regulation at 4-wk, and the temporal gene expression patterns were connected to the putative activity of SREBF1 and 2. In contrast, Cyp7a1, the gene responsible for the conversion of cholesterol to bile acids, was consistently up-regulated in the H-P/C-HF liver regardless of feeding duration. Over expression of Cyp7a1 after 2-d and 4-wk H-P/C-HF feeding was connected to two unique sets of transcription regulators. At both time points, up-regulation of the Cyp7a1 gene could be explained by enhanced activations and reduced suppressions of multiple transcription regulators. In conclusion, we demonstrated that the hypocholesterolemic effect of H-P/C-HF feeding coincided with orchestrated changes of gene expressions in lipid metabolic pathways in the liver of mice. Based on these results, we hypothesize that the cholesterol lowering effect of high-protein feeding is associated with enhanced bile acid production but clinical validation is warranted. (246 words).
authors.affiliation: Bioanalytical Science Department, Nestlé Research Center, Lausanne, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Raymond
authors.forename: Long
authors.initials: L
authors.lastname: Wang
authors.forename: Mireille
authors.initials: M
authors.lastname: Moser
authors.forename: Sylviane
authors.initials: S
authors.lastname: Metairon
authors.forename: Robert
authors.initials: R
authors.lastname: Mansourian
authors.forename: Marie-Camille
authors.initials: MC
authors.lastname: Zwahlen
authors.forename: Martin
authors.initials: M
authors.lastname: Kussmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Fuerholz
authors.forename: Katherine
authors.initials: K
authors.lastname: Macé
authors.forename: Chieh Jason
authors.initials: CJ
authors.lastname: Chou
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D059305:Diet, High-Fat; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004044:Dietary Proteins / Q000494:pharmacology*; D050171:Dyslipidemias / Q000150:complications / Q000378:metabolism / Q000473:pathology; D002149:Energy Intake / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013256:Steroids / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
chemical_list: D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D013256:Steroids; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase