Dietary fructose exacerbates hepatocellular injury when incorporated into a methionine-choline-deficient diet

Michael K. Pickens, Hisanobu Ogata, Russell K. Soon, James P. Grenert, Jacquelyn J. Maher

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: Methionine-choline-deficient (MCD) diets cause steatohepatitis in rodents and are used to model fatty liver disease in human beings. Recent studies have identified sucrose as a major contributor to MCD-related liver disease through its ability to promote hepatic de novo lipogenesis. Aims: To determine whether glucose and fructose, the two constitutents of sucrose, differ in their capacity to provoke steatohepatitis when incorporated individually into MCD formulas. Materials & Methods: MCD and control formulas prepared with either glucose or fructose as the sole source of carbohydrate were fed to mice for 21 days. Liver injury was assessed biochemically and histologically together with hepatic gene expression and fatty acid analysis. Results: Mice fed MCD formulas developed similar degrees of hepatic steatosis whether they contained glucose or fructose. By contrast, mice fed MCD-fructose developed significantly more hepatocellular injury than mice fed MCD-glucose, judged by histology, apoptosis staining and serum alanine aminotransferase. Liver injury in MCD-fructose mice coincided with an exaggerated rise in the ratio of long-chain saturated to unsaturated fatty acids in the liver. Notably, hepatic inflammation was not enhanced in mice fed MCD-fructose, correlating instead with hepatic lipid peroxidation, which was equivalent in the two MCD groups. Discussion: Fructose is more cytotoxic than glucose when used as the source of carbohydrate in MCD formulas. Conclusion: The data suggest the enhanced cytotoxicity of fructose in the MCD model is related to its ability to stimulate de novo lipogenesis, which yields harmful long-chain saturated fatty acids.

Original languageEnglish
Pages (from-to)1229-1239
Number of pages11
JournalLiver International
Volume30
Issue number8
DOIs
Publication statusPublished - Sep 1 2010

Fingerprint

Choline
Fructose
Methionine
Diet
Wounds and Injuries
Liver
Glucose
Fatty Liver
Lipogenesis
Sucrose
Liver Diseases
Fatty Acids
Carbohydrates
Alanine Transaminase
Unsaturated Fatty Acids
Lipid Peroxidation
Rodentia
Histology
Apoptosis
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Dietary fructose exacerbates hepatocellular injury when incorporated into a methionine-choline-deficient diet. / Pickens, Michael K.; Ogata, Hisanobu; Soon, Russell K.; Grenert, James P.; Maher, Jacquelyn J.

In: Liver International, Vol. 30, No. 8, 01.09.2010, p. 1229-1239.

Research output: Contribution to journalArticle

Pickens, Michael K. ; Ogata, Hisanobu ; Soon, Russell K. ; Grenert, James P. ; Maher, Jacquelyn J. / Dietary fructose exacerbates hepatocellular injury when incorporated into a methionine-choline-deficient diet. In: Liver International. 2010 ; Vol. 30, No. 8. pp. 1229-1239.
@article{f85353a9b1cc4e3bac4c58ee984ccdb7,
title = "Dietary fructose exacerbates hepatocellular injury when incorporated into a methionine-choline-deficient diet",
abstract = "Background: Methionine-choline-deficient (MCD) diets cause steatohepatitis in rodents and are used to model fatty liver disease in human beings. Recent studies have identified sucrose as a major contributor to MCD-related liver disease through its ability to promote hepatic de novo lipogenesis. Aims: To determine whether glucose and fructose, the two constitutents of sucrose, differ in their capacity to provoke steatohepatitis when incorporated individually into MCD formulas. Materials & Methods: MCD and control formulas prepared with either glucose or fructose as the sole source of carbohydrate were fed to mice for 21 days. Liver injury was assessed biochemically and histologically together with hepatic gene expression and fatty acid analysis. Results: Mice fed MCD formulas developed similar degrees of hepatic steatosis whether they contained glucose or fructose. By contrast, mice fed MCD-fructose developed significantly more hepatocellular injury than mice fed MCD-glucose, judged by histology, apoptosis staining and serum alanine aminotransferase. Liver injury in MCD-fructose mice coincided with an exaggerated rise in the ratio of long-chain saturated to unsaturated fatty acids in the liver. Notably, hepatic inflammation was not enhanced in mice fed MCD-fructose, correlating instead with hepatic lipid peroxidation, which was equivalent in the two MCD groups. Discussion: Fructose is more cytotoxic than glucose when used as the source of carbohydrate in MCD formulas. Conclusion: The data suggest the enhanced cytotoxicity of fructose in the MCD model is related to its ability to stimulate de novo lipogenesis, which yields harmful long-chain saturated fatty acids.",
author = "Pickens, {Michael K.} and Hisanobu Ogata and Soon, {Russell K.} and Grenert, {James P.} and Maher, {Jacquelyn J.}",
year = "2010",
month = "9",
day = "1",
doi = "10.1111/j.1478-3231.2010.02285.x",
language = "English",
volume = "30",
pages = "1229--1239",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Dietary fructose exacerbates hepatocellular injury when incorporated into a methionine-choline-deficient diet

AU - Pickens, Michael K.

AU - Ogata, Hisanobu

AU - Soon, Russell K.

AU - Grenert, James P.

AU - Maher, Jacquelyn J.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - Background: Methionine-choline-deficient (MCD) diets cause steatohepatitis in rodents and are used to model fatty liver disease in human beings. Recent studies have identified sucrose as a major contributor to MCD-related liver disease through its ability to promote hepatic de novo lipogenesis. Aims: To determine whether glucose and fructose, the two constitutents of sucrose, differ in their capacity to provoke steatohepatitis when incorporated individually into MCD formulas. Materials & Methods: MCD and control formulas prepared with either glucose or fructose as the sole source of carbohydrate were fed to mice for 21 days. Liver injury was assessed biochemically and histologically together with hepatic gene expression and fatty acid analysis. Results: Mice fed MCD formulas developed similar degrees of hepatic steatosis whether they contained glucose or fructose. By contrast, mice fed MCD-fructose developed significantly more hepatocellular injury than mice fed MCD-glucose, judged by histology, apoptosis staining and serum alanine aminotransferase. Liver injury in MCD-fructose mice coincided with an exaggerated rise in the ratio of long-chain saturated to unsaturated fatty acids in the liver. Notably, hepatic inflammation was not enhanced in mice fed MCD-fructose, correlating instead with hepatic lipid peroxidation, which was equivalent in the two MCD groups. Discussion: Fructose is more cytotoxic than glucose when used as the source of carbohydrate in MCD formulas. Conclusion: The data suggest the enhanced cytotoxicity of fructose in the MCD model is related to its ability to stimulate de novo lipogenesis, which yields harmful long-chain saturated fatty acids.

AB - Background: Methionine-choline-deficient (MCD) diets cause steatohepatitis in rodents and are used to model fatty liver disease in human beings. Recent studies have identified sucrose as a major contributor to MCD-related liver disease through its ability to promote hepatic de novo lipogenesis. Aims: To determine whether glucose and fructose, the two constitutents of sucrose, differ in their capacity to provoke steatohepatitis when incorporated individually into MCD formulas. Materials & Methods: MCD and control formulas prepared with either glucose or fructose as the sole source of carbohydrate were fed to mice for 21 days. Liver injury was assessed biochemically and histologically together with hepatic gene expression and fatty acid analysis. Results: Mice fed MCD formulas developed similar degrees of hepatic steatosis whether they contained glucose or fructose. By contrast, mice fed MCD-fructose developed significantly more hepatocellular injury than mice fed MCD-glucose, judged by histology, apoptosis staining and serum alanine aminotransferase. Liver injury in MCD-fructose mice coincided with an exaggerated rise in the ratio of long-chain saturated to unsaturated fatty acids in the liver. Notably, hepatic inflammation was not enhanced in mice fed MCD-fructose, correlating instead with hepatic lipid peroxidation, which was equivalent in the two MCD groups. Discussion: Fructose is more cytotoxic than glucose when used as the source of carbohydrate in MCD formulas. Conclusion: The data suggest the enhanced cytotoxicity of fructose in the MCD model is related to its ability to stimulate de novo lipogenesis, which yields harmful long-chain saturated fatty acids.

UR - http://www.scopus.com/inward/record.url?scp=79951638303&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951638303&partnerID=8YFLogxK

U2 - 10.1111/j.1478-3231.2010.02285.x

DO - 10.1111/j.1478-3231.2010.02285.x

M3 - Article

C2 - 20536716

AN - SCOPUS:79951638303

VL - 30

SP - 1229

EP - 1239

JO - Liver International

JF - Liver International

SN - 1478-3223

IS - 8

ER -