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Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice.
Biochem Biophys Res Commun. 2006 Apr 21; 342(4):1152-9.BB

Abstract

The biochemical differences between simple steatosis, a benign liver disease, and non-alcoholic steatohepatitis, which leads to cirrhosis, are unclear. Fat aussie is an obese mouse strain with a truncating mutation (foz) in the Alms1 gene. Chow-fed female foz/foz mice develop obesity, diabetes, and simple steatosis. We fed foz/foz and wildtype mice a high-fat diet. Foz/foz mice developed serum ALT elevation and severe steatohepatitis with hepatocyte ballooning, inflammation, and fibrosis; wildtype mice showed simple steatosis. Biochemical pathways favoring hepatocellular lipid accumulation (fatty acid uptake; lipogenesis) and lipid disposal (fatty acid beta-oxidation; triglyceride egress) were both induced by high-fat feeding in wildtype but not foz/foz mice. The resulting extremely high hepatic triglyceride levels were associated with induction of mitochondrial uncoupling protein-2 and adipocyte-specific fatty acid binding protein-2, but not cytochrome P4502e1 or lipid peroxidation. In this model of metabolic syndrome, transition of steatosis to steatohepatitis was associated with hypoadiponectinemia, a mediator of hepatic fatty acid disposal pathways.

Authors+Show Affiliations

John Curtin School of Medical Research, The Australian National University (ANU), Canberra, ACT, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16516152

Citation

Arsov, Todor, et al. "Adaptive Failure to High-fat Diet Characterizes Steatohepatitis in Alms1 Mutant Mice." Biochemical and Biophysical Research Communications, vol. 342, no. 4, 2006, pp. 1152-9.
Arsov T, Larter CZ, Nolan CJ, et al. Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice. Biochem Biophys Res Commun. 2006;342(4):1152-9.
Arsov, T., Larter, C. Z., Nolan, C. J., Petrovsky, N., Goodnow, C. C., Teoh, N. C., Yeh, M. M., & Farrell, G. C. (2006). Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice. Biochemical and Biophysical Research Communications, 342(4), 1152-9.
Arsov T, et al. Adaptive Failure to High-fat Diet Characterizes Steatohepatitis in Alms1 Mutant Mice. Biochem Biophys Res Commun. 2006 Apr 21;342(4):1152-9. PubMed PMID: 16516152.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice. AU - Arsov,Todor, AU - Larter,Claire Z, AU - Nolan,Christopher J, AU - Petrovsky,Nikolai, AU - Goodnow,Christopher C, AU - Teoh,Narcissus C, AU - Yeh,Matthew M, AU - Farrell,Geoffrey C, Y1 - 2006/02/20/ PY - 2006/01/16/received PY - 2006/02/07/accepted PY - 2006/3/7/pubmed PY - 2006/5/5/medline PY - 2006/3/7/entrez SP - 1152 EP - 9 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 342 IS - 4 N2 - The biochemical differences between simple steatosis, a benign liver disease, and non-alcoholic steatohepatitis, which leads to cirrhosis, are unclear. Fat aussie is an obese mouse strain with a truncating mutation (foz) in the Alms1 gene. Chow-fed female foz/foz mice develop obesity, diabetes, and simple steatosis. We fed foz/foz and wildtype mice a high-fat diet. Foz/foz mice developed serum ALT elevation and severe steatohepatitis with hepatocyte ballooning, inflammation, and fibrosis; wildtype mice showed simple steatosis. Biochemical pathways favoring hepatocellular lipid accumulation (fatty acid uptake; lipogenesis) and lipid disposal (fatty acid beta-oxidation; triglyceride egress) were both induced by high-fat feeding in wildtype but not foz/foz mice. The resulting extremely high hepatic triglyceride levels were associated with induction of mitochondrial uncoupling protein-2 and adipocyte-specific fatty acid binding protein-2, but not cytochrome P4502e1 or lipid peroxidation. In this model of metabolic syndrome, transition of steatosis to steatohepatitis was associated with hypoadiponectinemia, a mediator of hepatic fatty acid disposal pathways. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/16516152/Adaptive_failure_to_high_fat_diet_characterizes_steatohepatitis_in_Alms1_mutant_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(06)00312-3 DB - PRIME DP - Unbound Medicine ER -