Abstract

Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume20
Issue number7
DOIs
Publication statusPublished - Mar 29 2019

Fingerprint

coenzymes
Coenzymes
Lipogenesis
AMP-Activated Protein Kinases
Nifedipine
kidneys
Kidney
adenosine triphosphate
Adenosinetriphosphate
fatty acids
Fatty acids
Lipids
lipids
kidney diseases
cells
obesity
pathogenesis
fibrosis
Oxygen
oleic acid

Keywords

  • AMPK
  • calcium channel blockers
  • lipin-1
  • nifedipine
  • renal lipotoxicity
  • sterol regulatory element-binding proteins 1/2 (SREBP1/2)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway. / Lin, Yen Chung; Wu, Mai Szu; Lin, Yuh Feng; Chen, Chang Rong; Chen, Chang Yu; Chen, Chang Jui; Shen, Che Chou; Chen, Kuan Chou; Peng, Chiung Chi.

In: International Journal of Molecular Sciences, Vol. 20, No. 7, 29.03.2019.

Research output: Contribution to journalArticle

@article{d31009a7dc6942feaac59f70c86f8ae5,
title = "Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway",
abstract = "Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.",
keywords = "AMPK, calcium channel blockers, lipin-1, nifedipine, renal lipotoxicity, sterol regulatory element-binding proteins 1/2 (SREBP1/2)",
author = "Lin, {Yen Chung} and Wu, {Mai Szu} and Lin, {Yuh Feng} and Chen, {Chang Rong} and Chen, {Chang Yu} and Chen, {Chang Jui} and Shen, {Che Chou} and Chen, {Kuan Chou} and Peng, {Chiung Chi}",
year = "2019",
month = "3",
day = "29",
doi = "10.3390/ijms20071570",
language = "English",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "7",

}

TY - JOUR

T1 - Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway

AU - Lin, Yen Chung

AU - Wu, Mai Szu

AU - Lin, Yuh Feng

AU - Chen, Chang Rong

AU - Chen, Chang Yu

AU - Chen, Chang Jui

AU - Shen, Che Chou

AU - Chen, Kuan Chou

AU - Peng, Chiung Chi

PY - 2019/3/29

Y1 - 2019/3/29

N2 - Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.

AB - Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.

KW - AMPK

KW - calcium channel blockers

KW - lipin-1

KW - nifedipine

KW - renal lipotoxicity

KW - sterol regulatory element-binding proteins 1/2 (SREBP1/2)

UR - http://www.scopus.com/inward/record.url?scp=85064217365&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064217365&partnerID=8YFLogxK

U2 - 10.3390/ijms20071570

DO - 10.3390/ijms20071570

M3 - Article

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 7

ER -