Cytochrome P450, peroxisome proliferation, and cytoplasmic fatty acid binding protein content in liver, heart and kidney of the diabetic rat

Diabetes mellitus generally results in an increased systemic fatty acid mob ilization which can be associated with an increase in mitochondrial and per oxisomal beta-oxidation of fatty acids in selected tissues. The latter is u sually accompanied by a concomitant increase in the tissue content of cytop lasmic fatty acid-binding protein (FABP) which functions in the intracellul ar translocation of fatty acids, It was previously found that in liver clof ibrate-induced proliferation of peroxisomes and increase in FABP expression each are dependent on the induction by cytochrome P4504A1-mediated (CYP4A1 ) formation of dicarboxylic acids. We studied whether peroxisome proliferat ion and an increase of FABP contents in liver, heart and kidney of streptoz otocin-induced diabetic rats are also accompanied by an increase of CYP4A1 activity, as this would indicate a possible regulatory role for dicarboxyli c acids in peroxisome proliferation and FABP induction in diabetic organs o ther than liver. In livers of the diabetic rat, a concomitant increase was observed of the activities of CYP4A1 and the peroxisomal key enzyme fatty a cyl-CoA oxidase (FACO) and of the FABP content. Tn the diabetic heart FACO activity and FABP content also increased, but there was no induction of CYP 4A1 activity. Conversely, in diabetic kidney there was no increase in FACO activity nor FABP content in spite of a marked induction of CYP4A1 activity . It is concluded that streptozotocin-induced diabetes leads to increased p eroxisome proliferation and increased levels of FABP in both liver and hear t, which only in liver is accompanied by an induction of the cytochrome P45 0 system. Consequently, it is not likely that dicarboxylic acids are involv ed in the induction of peroxisome proliferation in the heart.