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Dietary phosphate restriction induces hepatic lipid accumulation through dysregulation of cholesterol metabolism in mice.
Nutr Res. 2013 Jul; 33(7):586-93.NR

Abstract

Excessive inorganic phosphate (Pi) intake and hyperphosphatemia have both been speculated to be risk factors for cardiovascular disease and hypercholesterolemia, and dysregulation of cholesterol metabolism can lead to atherosclerosis. However, the relationship between Pi and cholesterol metabolism has not been investigated in detail. Our recent study showed that triiodothyronine can induce both hyperphosphatemia and hypocholesterolemia in mice. We therefore hypothesized a possible linkage between Pi and cholesterol metabolism. In this study, we investigated the effects of dietary Pi intake on cholesterol metabolism in mice. Mice were divided into 4 groups, which were fed diets containing 1.2% or 0.1% Pi and with or without 2% cholesterol (Pi-sufficient, Pi-restricted, Pi-sufficient + Chol, and Pi-restricted + Chol), for 12 days. Inorganic phosphate-restricted mice exhibited significantly higher liver weights than did Pi-sufficient mice. Interestingly, dietary Pi restriction significantly increased high-cholesterol diet-induced hepatic lipid accumulation. Real-time polymerase chain reaction analysis revealed that dietary Pi restriction decreased expression of hepatic genes involved in cholesterol metabolism and fatty acid biosynthesis. In addition, hepatic messenger RNA levels of several transcription factors including peroxisome proliferator-activated receptors and liver X receptor were markedly decreased by Pi restriction. Furthermore, plasma lipid and lipoprotein profile analysis showed that dietary Pi restriction reduced susceptibility to high-cholesterol diet-induced hyperlipidemia. Importantly, we found that there was a significant negative correlation between plasma levels of Pi and total cholesterol. These results suggest that dietary Pi plays an important role in the development of fatty liver disease and hyperlipidemia induced by a high-cholesterol diet through regulation of lipid metabolism-related gene expression in the liver.

Authors+Show Affiliations

Department of Clinical Nutrition, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8503, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23827134

Citation

Tanaka, Sarasa, et al. "Dietary Phosphate Restriction Induces Hepatic Lipid Accumulation Through Dysregulation of Cholesterol Metabolism in Mice." Nutrition Research (New York, N.Y.), vol. 33, no. 7, 2013, pp. 586-93.
Tanaka S, Yamamoto H, Nakahashi O, et al. Dietary phosphate restriction induces hepatic lipid accumulation through dysregulation of cholesterol metabolism in mice. Nutr Res. 2013;33(7):586-93.
Tanaka, S., Yamamoto, H., Nakahashi, O., Kagawa, T., Ishiguro, M., Masuda, M., Kozai, M., Ikeda, S., Taketani, Y., & Takeda, E. (2013). Dietary phosphate restriction induces hepatic lipid accumulation through dysregulation of cholesterol metabolism in mice. Nutrition Research (New York, N.Y.), 33(7), 586-93. https://doi.org/10.1016/j.nutres.2013.05.004
Tanaka S, et al. Dietary Phosphate Restriction Induces Hepatic Lipid Accumulation Through Dysregulation of Cholesterol Metabolism in Mice. Nutr Res. 2013;33(7):586-93. PubMed PMID: 23827134.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary phosphate restriction induces hepatic lipid accumulation through dysregulation of cholesterol metabolism in mice. AU - Tanaka,Sarasa, AU - Yamamoto,Hironori, AU - Nakahashi,Otoki, AU - Kagawa,Tomohiro, AU - Ishiguro,Mariko, AU - Masuda,Masashi, AU - Kozai,Mina, AU - Ikeda,Shoko, AU - Taketani,Yutaka, AU - Takeda,Eiji, Y1 - 2013/06/10/ PY - 2012/11/12/received PY - 2013/04/13/revised PY - 2013/05/02/accepted PY - 2013/7/6/entrez PY - 2013/7/6/pubmed PY - 2014/1/22/medline KW - 1,25(OH)(2)D(3) KW - 1,25-dihydroxyvitamin D(3) KW - 3-hydroxy-3-methyl-glutaryl-CoA reductase KW - CKD KW - CVD KW - CYP7A1 KW - Cholesterol KW - Dietary phosphate KW - FGF-23 KW - FXR KW - Fatty liver KW - Gene expression KW - HDL KW - HMGC-R KW - HSL KW - LDL KW - LDL-R KW - LXR KW - Mice KW - Npt2a KW - PPARα KW - PPARγ KW - Pi KW - SCD1 KW - TG KW - VLDL KW - cardiovascular disease KW - cholesterol 7-α-monooxygenase or cytochrome P450 7A1 KW - chronic kidney disease KW - farnesoid X receptor KW - fibroblast growth factor-23 KW - high-density lipoprotein KW - hormone-sensitive lipase KW - inorganic phosphate KW - liver X receptor KW - low-density lipoprotein KW - low-density lipoprotein receptor KW - peroxisome proliferator–activated receptor α KW - peroxisome proliferator–activated receptor γ KW - stearoyl-CoA desaturase-1 KW - triglyceride KW - type IIa sodium-dependent phosphate cotransporter KW - very low density lipoprotein SP - 586 EP - 93 JF - Nutrition research (New York, N.Y.) JO - Nutr Res VL - 33 IS - 7 N2 - Excessive inorganic phosphate (Pi) intake and hyperphosphatemia have both been speculated to be risk factors for cardiovascular disease and hypercholesterolemia, and dysregulation of cholesterol metabolism can lead to atherosclerosis. However, the relationship between Pi and cholesterol metabolism has not been investigated in detail. Our recent study showed that triiodothyronine can induce both hyperphosphatemia and hypocholesterolemia in mice. We therefore hypothesized a possible linkage between Pi and cholesterol metabolism. In this study, we investigated the effects of dietary Pi intake on cholesterol metabolism in mice. Mice were divided into 4 groups, which were fed diets containing 1.2% or 0.1% Pi and with or without 2% cholesterol (Pi-sufficient, Pi-restricted, Pi-sufficient + Chol, and Pi-restricted + Chol), for 12 days. Inorganic phosphate-restricted mice exhibited significantly higher liver weights than did Pi-sufficient mice. Interestingly, dietary Pi restriction significantly increased high-cholesterol diet-induced hepatic lipid accumulation. Real-time polymerase chain reaction analysis revealed that dietary Pi restriction decreased expression of hepatic genes involved in cholesterol metabolism and fatty acid biosynthesis. In addition, hepatic messenger RNA levels of several transcription factors including peroxisome proliferator-activated receptors and liver X receptor were markedly decreased by Pi restriction. Furthermore, plasma lipid and lipoprotein profile analysis showed that dietary Pi restriction reduced susceptibility to high-cholesterol diet-induced hyperlipidemia. Importantly, we found that there was a significant negative correlation between plasma levels of Pi and total cholesterol. These results suggest that dietary Pi plays an important role in the development of fatty liver disease and hyperlipidemia induced by a high-cholesterol diet through regulation of lipid metabolism-related gene expression in the liver. SN - 1879-0739 UR - https://www.unboundmedicine.com/medline/citation/23827134/Dietary_phosphate_restriction_induces_hepatic_lipid_accumulation_through_dysregulation_of_cholesterol_metabolism_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0271-5317(13)00099-7 DB - PRIME DP - Unbound Medicine ER -