A snapshot of the hepatic transcriptome: Ad Libitum alcohol intake suppresses expression of cholesterol synthesis genes in alcohol-preferring (P) rats

Jonathon D. Klein, Jeremy B. Sherrill, Gabriella M. Morello, Phillip J. San Miguel, Zhenming Ding, Suthat Liangpunsakul, Tiebing Liang, William M. Muir, Lawrence Lumeng, Amy C. Lossie

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Research is uncovering the genetic and biochemical effects of consuming large quantities of alcohol. One prime example is the J- or U-shaped relationship between the levels of alcohol consumption and the risk of atherosclerotic cardiovascular disease. Moderate alcohol consumption in humans (about 30 g ethanol/d) is associated with reduced risk of coronary heart disease, while abstinence and heavier alcohol intake is linked to increased risk. However, the hepatic consequences of moderate alcohol drinking are largely unknown. Previous data from alcohol-preferring (P) rats showed that chronic consumption does not produce significant hepatic steatosis in this well-established model. Therefore, free-choice alcohol drinking in P rats may mimic low risk or nonhazardous drinking in humans, and chronic exposure in P animals can illuminate the molecular underpinnings of free-choice drinking in the liver. To address this gap, we captured the global, steady-state liver transcriptome following a 23 week free-choice, moderate alcohol consumption regimen (∼7.43 g ethanol/kg/day) in inbred alcohol-preferring (iP10a) rats. Chronic consumption led to down-regulation of nine genes in the cholesterol biosynthesis pathway, including HMG-CoA reductase, the rate-limiting step for cholesterol synthesis. These findings corroborate our phenotypic analyses, which indicate that this paradigm produced animals whose hepatic triglyceride levels, cholesterol levels and liver histology were indistinguishable from controls. These findings explain, at least in part, the J- or U-shaped relationship between cardiovascular risk and alcohol intake, and provide outstanding candidates for future studies aimed at understanding the mechanisms that underlie the salutary cardiovascular benefits of chronic low risk and nonhazardous alcohol intake.

Original languageEnglish
Article numbere110501
JournalPLoS One
Volume9
Issue number12
DOIs
StatePublished - Dec 26 2014

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Transcriptome
transcriptome
Rats
Alcohol Drinking
alcohols
Genes
Cholesterol
Alcohols
cholesterol
liver
synthesis
Liver
rats
genes
Drinking
Ethanol
drinking
Alcohol Abstinence
Hydroxymethylglutaryl CoA Reductases
ethanol

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A snapshot of the hepatic transcriptome : Ad Libitum alcohol intake suppresses expression of cholesterol synthesis genes in alcohol-preferring (P) rats. / Klein, Jonathon D.; Sherrill, Jeremy B.; Morello, Gabriella M.; San Miguel, Phillip J.; Ding, Zhenming; Liangpunsakul, Suthat; Liang, Tiebing; Muir, William M.; Lumeng, Lawrence; Lossie, Amy C.

In: PLoS One, Vol. 9, No. 12, e110501, 26.12.2014.

Research output: Contribution to journalArticle

Klein, Jonathon D. ; Sherrill, Jeremy B. ; Morello, Gabriella M. ; San Miguel, Phillip J. ; Ding, Zhenming ; Liangpunsakul, Suthat ; Liang, Tiebing ; Muir, William M. ; Lumeng, Lawrence ; Lossie, Amy C. / A snapshot of the hepatic transcriptome : Ad Libitum alcohol intake suppresses expression of cholesterol synthesis genes in alcohol-preferring (P) rats. In: PLoS One. 2014 ; Vol. 9, No. 12.
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