Back to Search
Start Over
Obesity-related fatty liver is unchanged in mice deficient for mitochondrial uncoupling protein 2.
- Source :
-
Hepatology (Baltimore, Md.) [Hepatology] 2002 Apr; Vol. 35 (4), pp. 753-61. - Publication Year :
- 2002
-
Abstract
- Nonalcoholic fatty liver disease (NAFLD), a prevalent condition associated with obesity, has the potential of evolving into end-stage liver disease. The biochemical mechanisms that define the progression of NAFLD are not well known, but reactive oxygen species (ROS) have been implicated in this process. Uncoupling protein (UCP) 2 is a mitochondrial inner-membrane protein that mediates proton leak, uncouples adenosine triphosphate (ATP) synthesis, and negatively regulates ROS production. UCP2 expression is increased in various animal models of NAFLD. Up-regulation of UCP2 may compromise cellular ATP levels and worsen liver damage, or it may be protective by ROS reduction in NAFLD. This study aimed to obtain a definitive answer as to whether increased UCP2 expression contributes to NAFLD. UCP2-/- mice were exposed to obesity by crossbreeding with ob/ob mice and by long-term high-fat feeding to study the effect of UCP2 deficiency on the outcome of NAFLD. Steatohepatitis score of crossbred mice (ob/ob/ko) was similar to that of ob/ob mice at 25 weeks. No compensatory increase was observed in the expression of UCP5 in ob/ob/ko livers. To unmask the effects of absent leptin and its potential proinflammatory actions, steatosis was also induced in UCP2-/- mice by a high-fat diet continued for 6 months. Serum alanine aminotransferase (ALT) levels remained normal, and the steatohepatitis score in UCP2-/- mice was the same as in wild-type controls. We conclude that increased expression of UCP2 in the livers of mice with genetically or diet-induced obesity exerts neither protective nor deleterious effects on the severity of fatty liver disease.
- Subjects :
- Animals
Carrier Proteins metabolism
Dietary Fats administration & dosage
Fatty Liver pathology
Ion Channels
Liver physiology
Mice
Mice, Knockout genetics
Mitochondrial Uncoupling Proteins
Nerve Tissue Proteins metabolism
Obesity genetics
Phenotype
Proteins genetics
Uncoupling Protein 2
Up-Regulation
Fatty Liver etiology
Membrane Transport Proteins
Mitochondrial Proteins
Obesity complications
Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0270-9139
- Volume :
- 35
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Hepatology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 11915020
- Full Text :
- https://doi.org/10.1053/jhep.2002.32028