Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model

Background & Aims In this study, we sought to determine the temporal relationship between hepatic mitochondrial dysfunction, hepatic steatosis and insulin resistance, and to examine their potential role in the natural progression of non-alcoholic fatty liver disease (NAFLD) utilising a sedentary...

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Bibliographic Details
Published in:Journal of hepatology 2010-05, Vol.52 (5), p.727-736
Main Authors: Rector, R. Scott, Thyfault, John P, Uptergrove, Grace M, Morris, E. Matthew, Naples, Scott P, Borengasser, Sarah J, Mikus, Catherine R, Laye, Matthew J, Laughlin, M. Harold, Booth, Frank W, Ibdah, Jamal A
Format: Article
Language:English
Subjects:
Adipose Tissue - physiopathology
Animals
Azo Compounds
Biological and medical sciences
Body Composition
Disease Models, Animal
Energy Intake
Fatty acid oxidation
Fatty Liver - physiopathology
Gastroenterology and Hepatology
Gastroenterology. Liver. Pancreas. Abdomen
Glutathione - metabolism
Glutathione Disulfide - metabolism
Insulin Resistance - physiology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Metabolic diseases
Mitochondria, Liver - physiology
Mitochondria, Liver - ultrastructure
Mitochondrial dysfunction
Non-alcoholic fatty liver disease
Obesity
Obesity - physiopathology
OLETF rat
Other diseases. Semiology
Oxidation-Reduction
Palmitic Acid - metabolism
Rats
Rats, Long-Evans
Reference Values
Superoxide Dismutase - metabolism
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Summary:Background & Aims In this study, we sought to determine the temporal relationship between hepatic mitochondrial dysfunction, hepatic steatosis and insulin resistance, and to examine their potential role in the natural progression of non-alcoholic fatty liver disease (NAFLD) utilising a sedentary, hyperphagic, obese, Otsuka Long–Evans Tokushima Fatty (OLETF) rat model. Methods OLETF rats and their non-hyperphagic control Long–Evans Tokushima Otsuka (LETO) rats were sacrificed at 5, 8, 13, 20, and 40 weeks of age ( n = 6–8 per group). Results At 5 weeks of age, serum insulin and glucose and hepatic triglyceride (TG) concentrations did not differ between animal groups; however, OLETF animals displayed significant ( p
ISSN:0168-8278
1600-0641
DOI:10.1016/j.jhep.2009.11.030