Isolated hypercholesterolemia leads to steatosis in the liver without affecting the pancreas

C. Csonka, Tamás Baranyai, L. Tiszlavicz, H. Fébel, Gergo Szucs, Zoltán V. Varga, Márta Sárközy, L. Puskás, Otilia Antal, Andrea Siska, I. Földesi, Péter Ferdinandy, L. Czakó, T. Csont

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Lipid accumulation in the liver and pancreas is primarily caused by combined hyperlipidemia. However, the effect of isolated hypercholesterolemia without hypertriglyceridemia is not fully described. Therefore, our aim was to investigate whether hypercholesterolemia alone leads to alterations both in hepatic and pancreatic lipid panel and histology in rats. Methods: Male Wistar rats were fed with 2% cholesterol +0.25% cholate-supplemented diet or standard chow for 12 weeks. Blood was collected at weeks 0, 4, 8 and 12 to measure serum cholesterol and triglyceride levels. At week 12, both the pancreas and the liver were isolated for further histological and biochemical analysis. Hepatic and plasma fatty acid composition was assessed by gas chromatography. Expression of mRNA of major enzymes involved in saturated/unsaturated fatty acid synthesis was analyzed by qPCR. In separate experiments serum enzyme activities and insulin levels were measured at week 9. Results: At week 12, rats fed with 2% cholesterol +0.25% cholate-supplemented diet were characterized by elevated serum cholesterol (4.09 ± 0.20 vs. 2.89 ± 0.22 mmol/L,p < 0.05) while triglyceride (2.27 ± 0.05 vs. 2.03 ± 0.03 mmol/L) and glucose levels (5.32 ± 0.14 vs. 5.23 ± 0.10 mmol/L) remained unchanged. Isolated hypercholesterolemia increased hepatic lipid accumulation, hepatic cholesterol (5.86 ± 0.22 vs. 1.60 ± 0.15 ng/g tissue,p < 0.05) and triglyceride contents (19.28 ± 1.42 vs. 6.78 ± 0.71 ng/g tissue,p < 0.05), and hepatic nitrotyrosine level (4.07 ± 0.52 vs. 2.59 ± 0.31 ng/mg protein,p < 0.05). The histology and tissue lipid content of the pancreas was not affected. Serum total protein level, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities remained unchanged in response to isolated hypercholesterolemia while serum alkaline phosphatase activity (ALP) significantly increased. Plasma insulin levels did not change in response to isolated hypercholesterolemia suggesting an intact endocrine function of the pancreas. Isolated hypercholesterolemia caused a significantly increased hepatic and serum fatty acid level associated with a marked alteration of fatty acid composition. Hepatic expression of Δ9-desaturase (SCD1) was increased 4.92×, while expression of Δ5-desaturase and Δ6-desaturase were decreased (0.447× and 0.577×, respectively) due to isolated hypercholesterolemia. Conclusions: Isolated hypercholesterolemia leads to hepatic steatosis and marked alterations in the hepatic lipid profile without affecting the pancreas. Altered fatty acid profile might mediate harmful effects of cholesterol in the liver.

Original languageEnglish
Article number144
JournalLipids in Health and Disease
Volume16
Issue number1
DOIs
Publication statusPublished - Jul 27 2017

Fingerprint

Fatty Liver
Hypercholesterolemia
Liver
Pancreas
Cholesterol
Lipids
Fatty Acids
Cholates
Rats
Triglycerides
Histology
Tissue
Nutrition
Insulin
Saturated fatty acids
Plasmas
Serum
Enzyme activity
Aspartate Aminotransferases
Chemical analysis

Keywords

  • Fatty acid desaturase (FADS)
  • Isolated hypercholesterolemia
  • Lipid droplets
  • Lipidomics
  • Lipotoxicity
  • Non-alcoholic fatty liver disease
  • Stearoyl-coenzyme a desaturase (SCD)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Isolated hypercholesterolemia leads to steatosis in the liver without affecting the pancreas. / Csonka, C.; Baranyai, Tamás; Tiszlavicz, L.; Fébel, H.; Szucs, Gergo; Varga, Zoltán V.; Sárközy, Márta; Puskás, L.; Antal, Otilia; Siska, Andrea; Földesi, I.; Ferdinandy, Péter; Czakó, L.; Csont, T.

In: Lipids in Health and Disease, Vol. 16, No. 1, 144, 27.07.2017.

Research output: Contribution to journalArticle

Csonka, C. ; Baranyai, Tamás ; Tiszlavicz, L. ; Fébel, H. ; Szucs, Gergo ; Varga, Zoltán V. ; Sárközy, Márta ; Puskás, L. ; Antal, Otilia ; Siska, Andrea ; Földesi, I. ; Ferdinandy, Péter ; Czakó, L. ; Csont, T. / Isolated hypercholesterolemia leads to steatosis in the liver without affecting the pancreas. In: Lipids in Health and Disease. 2017 ; Vol. 16, No. 1.
@article{45c1513adf5847649f83060196d97260,
title = "Isolated hypercholesterolemia leads to steatosis in the liver without affecting the pancreas",
abstract = "Background: Lipid accumulation in the liver and pancreas is primarily caused by combined hyperlipidemia. However, the effect of isolated hypercholesterolemia without hypertriglyceridemia is not fully described. Therefore, our aim was to investigate whether hypercholesterolemia alone leads to alterations both in hepatic and pancreatic lipid panel and histology in rats. Methods: Male Wistar rats were fed with 2{\%} cholesterol +0.25{\%} cholate-supplemented diet or standard chow for 12 weeks. Blood was collected at weeks 0, 4, 8 and 12 to measure serum cholesterol and triglyceride levels. At week 12, both the pancreas and the liver were isolated for further histological and biochemical analysis. Hepatic and plasma fatty acid composition was assessed by gas chromatography. Expression of mRNA of major enzymes involved in saturated/unsaturated fatty acid synthesis was analyzed by qPCR. In separate experiments serum enzyme activities and insulin levels were measured at week 9. Results: At week 12, rats fed with 2{\%} cholesterol +0.25{\%} cholate-supplemented diet were characterized by elevated serum cholesterol (4.09 ± 0.20 vs. 2.89 ± 0.22 mmol/L,p < 0.05) while triglyceride (2.27 ± 0.05 vs. 2.03 ± 0.03 mmol/L) and glucose levels (5.32 ± 0.14 vs. 5.23 ± 0.10 mmol/L) remained unchanged. Isolated hypercholesterolemia increased hepatic lipid accumulation, hepatic cholesterol (5.86 ± 0.22 vs. 1.60 ± 0.15 ng/g tissue,p < 0.05) and triglyceride contents (19.28 ± 1.42 vs. 6.78 ± 0.71 ng/g tissue,p < 0.05), and hepatic nitrotyrosine level (4.07 ± 0.52 vs. 2.59 ± 0.31 ng/mg protein,p < 0.05). The histology and tissue lipid content of the pancreas was not affected. Serum total protein level, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities remained unchanged in response to isolated hypercholesterolemia while serum alkaline phosphatase activity (ALP) significantly increased. Plasma insulin levels did not change in response to isolated hypercholesterolemia suggesting an intact endocrine function of the pancreas. Isolated hypercholesterolemia caused a significantly increased hepatic and serum fatty acid level associated with a marked alteration of fatty acid composition. Hepatic expression of Δ9-desaturase (SCD1) was increased 4.92×, while expression of Δ5-desaturase and Δ6-desaturase were decreased (0.447× and 0.577×, respectively) due to isolated hypercholesterolemia. Conclusions: Isolated hypercholesterolemia leads to hepatic steatosis and marked alterations in the hepatic lipid profile without affecting the pancreas. Altered fatty acid profile might mediate harmful effects of cholesterol in the liver.",
keywords = "Fatty acid desaturase (FADS), Isolated hypercholesterolemia, Lipid droplets, Lipidomics, Lipotoxicity, Non-alcoholic fatty liver disease, Stearoyl-coenzyme a desaturase (SCD)",
author = "C. Csonka and Tam{\'a}s Baranyai and L. Tiszlavicz and H. F{\'e}bel and Gergo Szucs and Varga, {Zolt{\'a}n V.} and M{\'a}rta S{\'a}rk{\"o}zy and L. Pusk{\'a}s and Otilia Antal and Andrea Siska and I. F{\"o}ldesi and P{\'e}ter Ferdinandy and L. Czak{\'o} and T. Csont",
year = "2017",
month = "7",
day = "27",
doi = "10.1186/s12944-017-0537-z",
language = "English",
volume = "16",
journal = "Lipids in Health and Disease",
issn = "1476-511X",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Isolated hypercholesterolemia leads to steatosis in the liver without affecting the pancreas

AU - Csonka, C.

AU - Baranyai, Tamás

AU - Tiszlavicz, L.

AU - Fébel, H.

AU - Szucs, Gergo

AU - Varga, Zoltán V.

AU - Sárközy, Márta

AU - Puskás, L.

AU - Antal, Otilia

AU - Siska, Andrea

AU - Földesi, I.

AU - Ferdinandy, Péter

AU - Czakó, L.

AU - Csont, T.

PY - 2017/7/27

Y1 - 2017/7/27

N2 - Background: Lipid accumulation in the liver and pancreas is primarily caused by combined hyperlipidemia. However, the effect of isolated hypercholesterolemia without hypertriglyceridemia is not fully described. Therefore, our aim was to investigate whether hypercholesterolemia alone leads to alterations both in hepatic and pancreatic lipid panel and histology in rats. Methods: Male Wistar rats were fed with 2% cholesterol +0.25% cholate-supplemented diet or standard chow for 12 weeks. Blood was collected at weeks 0, 4, 8 and 12 to measure serum cholesterol and triglyceride levels. At week 12, both the pancreas and the liver were isolated for further histological and biochemical analysis. Hepatic and plasma fatty acid composition was assessed by gas chromatography. Expression of mRNA of major enzymes involved in saturated/unsaturated fatty acid synthesis was analyzed by qPCR. In separate experiments serum enzyme activities and insulin levels were measured at week 9. Results: At week 12, rats fed with 2% cholesterol +0.25% cholate-supplemented diet were characterized by elevated serum cholesterol (4.09 ± 0.20 vs. 2.89 ± 0.22 mmol/L,p < 0.05) while triglyceride (2.27 ± 0.05 vs. 2.03 ± 0.03 mmol/L) and glucose levels (5.32 ± 0.14 vs. 5.23 ± 0.10 mmol/L) remained unchanged. Isolated hypercholesterolemia increased hepatic lipid accumulation, hepatic cholesterol (5.86 ± 0.22 vs. 1.60 ± 0.15 ng/g tissue,p < 0.05) and triglyceride contents (19.28 ± 1.42 vs. 6.78 ± 0.71 ng/g tissue,p < 0.05), and hepatic nitrotyrosine level (4.07 ± 0.52 vs. 2.59 ± 0.31 ng/mg protein,p < 0.05). The histology and tissue lipid content of the pancreas was not affected. Serum total protein level, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities remained unchanged in response to isolated hypercholesterolemia while serum alkaline phosphatase activity (ALP) significantly increased. Plasma insulin levels did not change in response to isolated hypercholesterolemia suggesting an intact endocrine function of the pancreas. Isolated hypercholesterolemia caused a significantly increased hepatic and serum fatty acid level associated with a marked alteration of fatty acid composition. Hepatic expression of Δ9-desaturase (SCD1) was increased 4.92×, while expression of Δ5-desaturase and Δ6-desaturase were decreased (0.447× and 0.577×, respectively) due to isolated hypercholesterolemia. Conclusions: Isolated hypercholesterolemia leads to hepatic steatosis and marked alterations in the hepatic lipid profile without affecting the pancreas. Altered fatty acid profile might mediate harmful effects of cholesterol in the liver.

AB - Background: Lipid accumulation in the liver and pancreas is primarily caused by combined hyperlipidemia. However, the effect of isolated hypercholesterolemia without hypertriglyceridemia is not fully described. Therefore, our aim was to investigate whether hypercholesterolemia alone leads to alterations both in hepatic and pancreatic lipid panel and histology in rats. Methods: Male Wistar rats were fed with 2% cholesterol +0.25% cholate-supplemented diet or standard chow for 12 weeks. Blood was collected at weeks 0, 4, 8 and 12 to measure serum cholesterol and triglyceride levels. At week 12, both the pancreas and the liver were isolated for further histological and biochemical analysis. Hepatic and plasma fatty acid composition was assessed by gas chromatography. Expression of mRNA of major enzymes involved in saturated/unsaturated fatty acid synthesis was analyzed by qPCR. In separate experiments serum enzyme activities and insulin levels were measured at week 9. Results: At week 12, rats fed with 2% cholesterol +0.25% cholate-supplemented diet were characterized by elevated serum cholesterol (4.09 ± 0.20 vs. 2.89 ± 0.22 mmol/L,p < 0.05) while triglyceride (2.27 ± 0.05 vs. 2.03 ± 0.03 mmol/L) and glucose levels (5.32 ± 0.14 vs. 5.23 ± 0.10 mmol/L) remained unchanged. Isolated hypercholesterolemia increased hepatic lipid accumulation, hepatic cholesterol (5.86 ± 0.22 vs. 1.60 ± 0.15 ng/g tissue,p < 0.05) and triglyceride contents (19.28 ± 1.42 vs. 6.78 ± 0.71 ng/g tissue,p < 0.05), and hepatic nitrotyrosine level (4.07 ± 0.52 vs. 2.59 ± 0.31 ng/mg protein,p < 0.05). The histology and tissue lipid content of the pancreas was not affected. Serum total protein level, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities remained unchanged in response to isolated hypercholesterolemia while serum alkaline phosphatase activity (ALP) significantly increased. Plasma insulin levels did not change in response to isolated hypercholesterolemia suggesting an intact endocrine function of the pancreas. Isolated hypercholesterolemia caused a significantly increased hepatic and serum fatty acid level associated with a marked alteration of fatty acid composition. Hepatic expression of Δ9-desaturase (SCD1) was increased 4.92×, while expression of Δ5-desaturase and Δ6-desaturase were decreased (0.447× and 0.577×, respectively) due to isolated hypercholesterolemia. Conclusions: Isolated hypercholesterolemia leads to hepatic steatosis and marked alterations in the hepatic lipid profile without affecting the pancreas. Altered fatty acid profile might mediate harmful effects of cholesterol in the liver.

KW - Fatty acid desaturase (FADS)

KW - Isolated hypercholesterolemia

KW - Lipid droplets

KW - Lipidomics

KW - Lipotoxicity

KW - Non-alcoholic fatty liver disease

KW - Stearoyl-coenzyme a desaturase (SCD)

UR - http://www.scopus.com/inward/record.url?scp=85026198243&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026198243&partnerID=8YFLogxK

U2 - 10.1186/s12944-017-0537-z

DO - 10.1186/s12944-017-0537-z

M3 - Article

VL - 16

JO - Lipids in Health and Disease

JF - Lipids in Health and Disease

SN - 1476-511X

IS - 1

M1 - 144

ER -