Niacin improves renal lipid metabolism and slows progression in chronic kidney disease.
BACKGROUND
Mounting evidence points to lipid accumulation in the diseased kidney and its contribution to progression of nephropathy. We recently found heavy lipid accumulation and marked dysregulation of lipid metabolism in the remnant kidneys of rats with chronic renal failure (CRF). Present study sought to determine efficacy of niacin supplementation on renal tissue lipid metabolism in CRF.


METHODS
Kidney function, lipid content, and expression of molecules involved in cholesterol and fatty acid metabolism were determined in untreated CRF (5/6 nephrectomized), niacin-treated CRF (50 mg/kg/day in drinking water for 12 weeks) and control rats.


RESULTS
CRF resulted in hypertension, proteinuria, renal tissue lipid accumulation, up-regulation of scavenger receptor A1 (SR-A1), acyl-CoA cholesterol acyltransferase-1 (ACAT1), carbohydrate-responsive element binding protein (ChREBP), fatty acid synthase (FAS), acyl-CoA carboxylase (ACC), liver X receptor (LXR), ATP binding cassette (ABC) A-1, ABCG-1, and SR-B1 and down-regulation of sterol responsive element binding protein-1 (SREBP-1), SREBP-2, HMG-CoA reductase, PPAR-alpha, fatty acid binding protein (L-FABP), and CPT1A. Niacin therapy attenuated hypertension, proteinuria, and tubulo-interstitial injury, reduced renal tissue lipids, CD36, ChREBP, LXR, ABCA-1, ABCG-1, and SR-B1 abundance and raised PPAR-alpha and L-FABP.


CONCLUSIONS
Niacin administration improves renal tissue lipid metabolism and renal function and structure in experimental CRF.
Cho
Kyu-hyang
KH
Division of Nephrology and Hypertension, University of California, Irvine, Irvine, CA, USA.
Kim
Hyun-ju
HJ
Kamanna
Vaijinath S
VS
Vaziri
Nosratola D
ND
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism; D019587:Dietary Supplements; D018450:Disease Progression; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D000071518:Liver X Receptors; D008297:Male; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000494:pharmacology
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018955:CD36 Antigens; C008132:Cd36 protein, rat; D050556:Fatty Acid-Binding Proteins; D008055:Lipids; D000071518:Liver X Receptors; C442825:Mlxipl protein, rat; D057093:Orphan Nuclear Receptors; D047493:PPAR alpha; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D014803:Vitamin B Complex; D009525:Niacin