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A proteome analysis of livers from obese ( ob/ob ) mice treated with the peroxisome proliferator WY14,643
Author(s) -
Edvardsson Ulrika,
Alexandersson Maria,
Brockenhuus von Löwenhielm Helena,
Nyström AnnChristin,
Ljung Bengt,
Nilsson Fredrik,
Dahllöf Björn
Publication year - 1999
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/(sici)1522-2683(19990101)20:4/5<935::aid-elps935>3.0.co;2-6
Subject(s) - endocrinology , medicine , peroxisome proliferator activated receptor , peroxisome , lipid metabolism , insulin resistance , receptor , glucose homeostasis , adipose tissue , agonist , adipocyte , chemistry , rosiglitazone , fatty acid metabolism , beta oxidation , insulin , biology , metabolism
The PPAR (peroxisome proliferator activated receptor) transcription factors are ligand‐activated receptors which regulate genes involved in lipid metabolism and homeostasis. PPARα is preferentially expressed in the liver and PPARγ preferentially in adipose tissue. Activation of PPARα leads to peroxisome proliferation in rodents and increased β‐oxidation of fatty acids. PPARγ‐activation leads to adipocyte differentiation and improved insulin signaling of mature adipocytes. Both of these PPAR receptors are potential targets for treatment of dyslipidemia in man. Studies by others using a proteomics approach have characterized the effects of PPARα agonists in livers from lean healthy mice. However, we wanted to map the effects of a therapeutic dose of a PPARα agonist in a disease model of insulin resistance and diabetes, the obese diabetic ob/ob mouse, by proteomics. Therefore, ob/ob mice, which have highly elevated levels of plasma triglycerides, glucose and insulin, were treated for one week with WY14,643 (180 μmol/kg/day), a well‐characterized selective PPARα agonist. Plasma triglycerides, glucose and insulin levels were determined and we found significant therapeutic effects on triglycerides and glucose levels. The liver protein compositions were investigated by high‐resolution two‐dimensional gel electrophoresis which showed that WY14,643 produced up‐regulation of at least 16 spots. These were identified by mass spectrometry and 14 spots were found to be components of the peroxisomal fatty acid metabolism. Thus, WY14,643 at a therapeutic dose, caused induction of peroxisomal fatty acid β‐oxidation in obese diabetic mice.