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Dietary saturated fats cause acute upregulation of transcriptional factors that modulate lipid synthetic pathways in the kidney
Author(s) -
Jiang Tao,
Li Jinping,
Levi Moshe
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a524
Subject(s) - fatty acid synthase , medicine , saturated fat , endocrinology , sterol regulatory element binding protein , saturated fatty acid , cholesterol , carbohydrate responsive element binding protein , chemistry , hmg coa reductase , kidney , downregulation and upregulation , fatty acid synthesis , sterol , fatty acid , lipid metabolism , reductase , biology , enzyme , biochemistry , transcription factor , gene
Administration of a saturated fat enriched diet has been shown to paradoxically induce liver fatty acid and cholesterol synthetic pathways resulting increased liver lipid content. The response of the kidney to a saturated fat enriched diet however is not known. We fed C57Bl/6 male mice a control diet or a saturated fat enriched diet for 1 day, 3 days and 7 days. We found that as early as 24 hrs following feeding a saturated fat enriched diet there are marked increases in: i) the sterol regulatory element binding protein‐1c (SREBP‐1c) and its major target enzymes acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) mRNA levels, ii) the carbohydrate response element binding protein (ChREBP) and its major target enzyme L‐PK mRNA levels, and iii) the sterol regulatory element binding protein‐2 (SREBP‐2) and its major target enzyme HMG CoA Reductase mRNA levels. These responses are sustained throughout the experimental period and long‐term feeding of saturated fat enriched diet results in glomerulosclerosis and proteinuria. Interestingly treatment of glomerular mesangial cells with saturated fatty acids also result in a similar response with increases in SREBP‐1c and SREBP‐2 mRNA levels and accumulation of lipids. Our results therefore indicate that dietary saturated fats induce increased renal expression of key transcriptional factors including ChREBP, SREBP‐1c and SREBP‐2 that mediate fatty acid and cholesterol synthesis, modulate lipid composition of the kidney, and cause glomerular injury.