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)

High dietary protein decreases fat deposition induced by high-fat and high-sucrose diet in rats

“…Increasing dietary protein reduces lipid accumulation in the liver ( 1 – 4 ) and in the adipose tissue (AT) ( 2 , 5 ) . These effects have been attributed to a reduced energy intake due to the satiating effect of proteins ( 6 , 7 ) , but it was also observed in pair-fed rats ( 8 ) and in ad libitum- fed mice ( 1 ) that a reduced fat mass can be observed without differences in energy intake.…”

Biological Activities, Health Benefits, and Therapeutic Properties of Avenanthramides: From Skin Protection to Prevention and Treatment of Cerebrovascular Diseases

“…Thus, it is possible to formulate dietary recommendations based on a system biology perspective to ensure a healthy condition or to prevent and treat chronic diseases, such as CVDs, obesity, and cancer [ 103 ]. In this context, we particularly underline the importance of foodomics studies that over time have been performed on human, animals, and animal models of human diseases administered with (i) rosemary extracts rich in polyphenols [ 104 – 106 ] and corresponding isolated metabolite carnosol and carnosic acid [ 107 , 108 ]; (ii) red-to-blue fruit extracts rich in anthocyanins [ 109 ]; (iii) vegetable extracts rich in flavonoids [ 110 ] and isoflavones or isolated genistein, daidzein [ 111 ], and flavone [ 112 ]; (iv) green tea extracts rich in polyphenols [ 113 ]; (v) olive oil extracts rich in polyphenols [ 114 ]; (vi) fish oil extracts rich in polyunsaturated fatty acids [ 115 ]; (vii) resveratrol-containing foods [ 116 ]; (viii) inulin-containing prebiotics and isolated inulin; (ix) increased dietary protein [ 117 , 118 ]; (x) nutrients lacking normal Zn supplement [ 119 ]; (xi) augmented folate [ 120 ] and multivitamin/mineral supplement [ 121 ]. Due to the complexity of these studies, their results were often published in different articles.…”

Influence of plasma macronutrient levels on hepatic metabolism: role of regulatory networks in homeostasis and disease states

“…These effect of low carbohydrate, high fat and high protein diet on cholesterol homeostasis in mice was also documented. 67 Higher levels of amino acids inhibits the AKT mediated activation of SREBP thereby reducing the ux through cholesterol synthesis. The observation suggested that, higher levels of plasma amino acids under a diabetic state can help in reducing the HMG-CoA reductase ux there by reducing hypercholesterolemia.…”