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Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA desaturases 1 and 2

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Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA desaturases 1 and 2. / Sieber, Jonas; Weins, Astrid; Kampe, Kapil; Gruber, Stefan; Lindenmeyer, Maja T; Cohen, Clemens D; Orellana, Jana M; Mundel, Peter; Jehle, Andreas W.

In: AM J PATHOL, Vol. 183, No. 3, 09.2013, p. 735-44.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sieber, J, Weins, A, Kampe, K, Gruber, S, Lindenmeyer, MT, Cohen, CD, Orellana, JM, Mundel, P & Jehle, AW 2013, 'Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA desaturases 1 and 2', AM J PATHOL, vol. 183, no. 3, pp. 735-44. https://doi.org/10.1016/j.ajpath.2013.05.023

APA

Sieber, J., Weins, A., Kampe, K., Gruber, S., Lindenmeyer, M. T., Cohen, C. D., Orellana, J. M., Mundel, P., & Jehle, A. W. (2013). Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA desaturases 1 and 2. AM J PATHOL, 183(3), 735-44. https://doi.org/10.1016/j.ajpath.2013.05.023

Vancouver

Sieber J, Weins A, Kampe K, Gruber S, Lindenmeyer MT, Cohen CD et al. Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA desaturases 1 and 2. AM J PATHOL. 2013 Sep;183(3):735-44. https://doi.org/10.1016/j.ajpath.2013.05.023

Bibtex

@article{77d2daa26e1743719c9ef8b606415ca0,
title = "Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA desaturases 1 and 2",
abstract = "Type 2 diabetes mellitus is characterized by dyslipidemia with elevated free fatty acids (FFAs). Loss of podocytes is a hallmark of diabetic nephropathy, and podocytes are highly susceptible to saturated FFAs but not to protective, monounsaturated FFAs. We report that patients with diabetic nephropathy develop alterations in glomerular gene expression of enzymes involved in fatty acid metabolism, including induction of stearoyl-CoA desaturase (SCD)-1, which converts saturated to monounsaturated FFAs. By IHC of human renal biopsy specimens, glomerular SCD-1 induction was observed in podocytes of patients with diabetic nephropathy. Functionally, the liver X receptor agonists TO901317 and GW3965, two known inducers of SCD, increased Scd-1 and Scd-2 expression in cultured podocytes and reduced palmitic acid-induced cell death. Similarly, overexpression of Scd-1 attenuated palmitic acid-induced cell death. The protective effect of TO901317 was associated with a reduction of endoplasmic reticulum stress. It was lost after gene silencing of Scd-1/-2, thereby confirming that the protective effect of TO901317 is mediated by Scd-1/-2. TO901317 also shifted palmitic acid-derived FFAs into biologically inactive triglycerides. In summary, SCD-1 up-regulation in diabetic nephropathy may be part of a protective mechanism against saturated FFA-derived toxic metabolites that drive endoplasmic reticulum stress and podocyte death. ",
keywords = "Benzoates, Benzylamines, Carnitine O-Palmitoyltransferase, Cell Death, Cells, Cultured, Diabetic Nephropathies, Fatty Acids, Monounsaturated, Gene Expression Regulation, Gene Knockdown Techniques, Gene Silencing, Humans, Hydrocarbons, Fluorinated, Kidney Glomerulus, Models, Biological, Oxidation-Reduction, Palmitic Acid, Podocytes, Protective Agents, Stearoyl-CoA Desaturase, Sulfonamides, Triglycerides, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Jonas Sieber and Astrid Weins and Kapil Kampe and Stefan Gruber and Lindenmeyer, {Maja T} and Cohen, {Clemens D} and Orellana, {Jana M} and Peter Mundel and Jehle, {Andreas W}",
note = "Copyright {\textcopyright} 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.",
year = "2013",
month = sep,
doi = "10.1016/j.ajpath.2013.05.023",
language = "English",
volume = "183",
pages = "735--44",
journal = "AM J PATHOL",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA desaturases 1 and 2

AU - Sieber, Jonas

AU - Weins, Astrid

AU - Kampe, Kapil

AU - Gruber, Stefan

AU - Lindenmeyer, Maja T

AU - Cohen, Clemens D

AU - Orellana, Jana M

AU - Mundel, Peter

AU - Jehle, Andreas W

N1 - Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PY - 2013/9

Y1 - 2013/9

N2 - Type 2 diabetes mellitus is characterized by dyslipidemia with elevated free fatty acids (FFAs). Loss of podocytes is a hallmark of diabetic nephropathy, and podocytes are highly susceptible to saturated FFAs but not to protective, monounsaturated FFAs. We report that patients with diabetic nephropathy develop alterations in glomerular gene expression of enzymes involved in fatty acid metabolism, including induction of stearoyl-CoA desaturase (SCD)-1, which converts saturated to monounsaturated FFAs. By IHC of human renal biopsy specimens, glomerular SCD-1 induction was observed in podocytes of patients with diabetic nephropathy. Functionally, the liver X receptor agonists TO901317 and GW3965, two known inducers of SCD, increased Scd-1 and Scd-2 expression in cultured podocytes and reduced palmitic acid-induced cell death. Similarly, overexpression of Scd-1 attenuated palmitic acid-induced cell death. The protective effect of TO901317 was associated with a reduction of endoplasmic reticulum stress. It was lost after gene silencing of Scd-1/-2, thereby confirming that the protective effect of TO901317 is mediated by Scd-1/-2. TO901317 also shifted palmitic acid-derived FFAs into biologically inactive triglycerides. In summary, SCD-1 up-regulation in diabetic nephropathy may be part of a protective mechanism against saturated FFA-derived toxic metabolites that drive endoplasmic reticulum stress and podocyte death.

AB - Type 2 diabetes mellitus is characterized by dyslipidemia with elevated free fatty acids (FFAs). Loss of podocytes is a hallmark of diabetic nephropathy, and podocytes are highly susceptible to saturated FFAs but not to protective, monounsaturated FFAs. We report that patients with diabetic nephropathy develop alterations in glomerular gene expression of enzymes involved in fatty acid metabolism, including induction of stearoyl-CoA desaturase (SCD)-1, which converts saturated to monounsaturated FFAs. By IHC of human renal biopsy specimens, glomerular SCD-1 induction was observed in podocytes of patients with diabetic nephropathy. Functionally, the liver X receptor agonists TO901317 and GW3965, two known inducers of SCD, increased Scd-1 and Scd-2 expression in cultured podocytes and reduced palmitic acid-induced cell death. Similarly, overexpression of Scd-1 attenuated palmitic acid-induced cell death. The protective effect of TO901317 was associated with a reduction of endoplasmic reticulum stress. It was lost after gene silencing of Scd-1/-2, thereby confirming that the protective effect of TO901317 is mediated by Scd-1/-2. TO901317 also shifted palmitic acid-derived FFAs into biologically inactive triglycerides. In summary, SCD-1 up-regulation in diabetic nephropathy may be part of a protective mechanism against saturated FFA-derived toxic metabolites that drive endoplasmic reticulum stress and podocyte death.

KW - Benzoates

KW - Benzylamines

KW - Carnitine O-Palmitoyltransferase

KW - Cell Death

KW - Cells, Cultured

KW - Diabetic Nephropathies

KW - Fatty Acids, Monounsaturated

KW - Gene Expression Regulation

KW - Gene Knockdown Techniques

KW - Gene Silencing

KW - Humans

KW - Hydrocarbons, Fluorinated

KW - Kidney Glomerulus

KW - Models, Biological

KW - Oxidation-Reduction

KW - Palmitic Acid

KW - Podocytes

KW - Protective Agents

KW - Stearoyl-CoA Desaturase

KW - Sulfonamides

KW - Triglycerides

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ajpath.2013.05.023

DO - 10.1016/j.ajpath.2013.05.023

M3 - SCORING: Journal article

C2 - 23867797

VL - 183

SP - 735

EP - 744

JO - AM J PATHOL

JF - AM J PATHOL

SN - 0002-9440

IS - 3

ER -