Precision-cut liver slices from diet-induced obese rats exposed to ethanol are susceptible to oxidative stress and increased fatty acid synthesis

Michael J. Duryee, Monte Willis, Courtney S. Schaffert, Roger D. Reidelberger, Anand Dusad, Daniel R. Anderson, Lynell W. Klassen, Geoffrey M. Thiele

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Oxidative stress from fat accumulation in the liver has many deleterious effects. Many believe that there is a second hit that causes relatively benign fat accumulation to transform into liver failure. Therefore, we evaluated the effects of ethanol on ex vivo precision-cut liver slice cultures (PCLS) from rats fed a high-fat diet resulting in fatty liver. Agematched male Sprague-Dawley rats were fed either high-fat (obese) (45% calories from fat, 4.73 kcal/g) or control diet for 13 mo. PCLS were prepared, incubated with 25 mM ethanol for 24, 48, and 72 h, harvested, and evaluated for ethanol metabolism, triglyceride production, oxidative stress, and cytokine expression. Ethanol metabolism and acetaldehyde production decreased in PCLS from obese rats compared with age-matched controls (AMC). Increased triglyceride and smooth muscle actin production was observed in PCLS from obese rats compared with AMC, which further increased following ethanol incubation. Lipid peroxidation, measured by thiobarbituric acid reactive substances assay, increased in response to ethanol, whereas GSH and heme oxygenase I levels were decreased. TNF-α and IL-6 levels were increased in the PCLS from obese rats and increased further with ethanol incubation. Diet-induced fatty liver increases the susceptibility of the liver to toxins such as ethanol, possibly by the increased oxidative stress and cytokine production. These findings support the concept that the development of fatty liver sensitizes the liver to the effects of ethanol and leads to the start of liver failure, necrosis, and eventually cirrhosis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume306
Issue number3
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

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Oxidative Stress
Ethanol
Fatty Acids
Diet
Liver
Fatty Liver
Fats
Liver Failure
Triglycerides
Cytokines
Heme Oxygenase (Decyclizing)
Acetaldehyde
Thiobarbituric Acid Reactive Substances
High Fat Diet
Lipid Peroxidation
Smooth Muscle
Sprague Dawley Rats
Actins
Interleukin-6
Fibrosis

Keywords

  • Alcohol liver disease
  • Fatty liver disease
  • Obesity
  • Oxidative stress
  • Precision-cut liver slices

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

Precision-cut liver slices from diet-induced obese rats exposed to ethanol are susceptible to oxidative stress and increased fatty acid synthesis. / Duryee, Michael J.; Willis, Monte; Schaffert, Courtney S.; Reidelberger, Roger D.; Dusad, Anand; Anderson, Daniel R.; Klassen, Lynell W.; Thiele, Geoffrey M.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 306, No. 3, 01.02.2014.

Research output: Contribution to journalArticle

Duryee, Michael J. ; Willis, Monte ; Schaffert, Courtney S. ; Reidelberger, Roger D. ; Dusad, Anand ; Anderson, Daniel R. ; Klassen, Lynell W. ; Thiele, Geoffrey M. / Precision-cut liver slices from diet-induced obese rats exposed to ethanol are susceptible to oxidative stress and increased fatty acid synthesis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2014 ; Vol. 306, No. 3.
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