Microsomal and peroxisomal fatty acid oxidation in streptozotocin diabetic rat liver
Department of Biochemistry, Faculty of Medicine, University of Chile, Santiago, Chile.General Pharmacology 04/1997; 28(3):361-4. DOI: 10.1016/S0306-3623(96)00231-5
Microsomal lauric acid hydroxylation and fatty acid peroxisomal beta-oxidation were studied in hepatic subcellulant preparations from streptozotocin-induced diabetic and diabetic insulin-treated rats. 2. The liver microsomes of the streptozotocin diabetic rats displayed a similar activity to hydroxylate lauric acid as the control microsomes. 3. Diabetic insulin-treated rats showed lower (omega 1) and omega-lauric acid hydroxylase activities than diabetic and control rats. 4. Streptozotocin-induced diabetes and diabetic insulin-treated rats exhibited no significant changes on peroxisomal palmitoyl CoA beta-oxidation compared to the control rats. 5. Both microsomal and peroxisomal fatty acid oxidation responded in a similar way in this model of experimental diabetes.
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ABSTRACT: Peroxisomal oxidation yields metabolites that are more efficiently utilized by mitochondria. This is of potential clinical importance because reduced fatty acid oxidation is suspected to promote excess lipid accumulation in obesity-associated insulin resistance. Our purpose was to assess peroxisomal contributions to mitochondrial oxidation in mixed gastrocnemius (MG), liver, and left ventricle (LV) homogenates from lean and fatty (fa/fa) Zucker rats. Results indicate that complete mitochondrial oxidation (CO(2) production) using various lipid substrates was increased approximately twofold in MG, unaltered in LV, and diminished approximately 50% in liver of fa/fa rats. In isolated mitochondria, malonyl-CoA inhibited CO(2) production from palmitate 78%, whereas adding isolated peroxisomes reduced inhibition to 21%. These data demonstrate that peroxisomal products may enter mitochondria independently of CPT I, thus providing a route to maintain lipid disposal under conditions where malonyl-CoA levels are elevated, such as in insulin-resistant tissues. Peroxisomal metabolism of lignoceric acid in fa/fa rats was elevated in both liver and MG (LV unaltered), but peroxisomal product distribution varied. A threefold elevation in incomplete oxidation was solely responsible for increased hepatic peroxisomal oxidation (CO(2) unaltered). Alternatively, only CO(2) was detected in MG, indicating that peroxisomal products were exclusively partitioned to mitochondria for complete lipid disposal. These data suggest tissue-specific destinations for peroxisome-derived products and emphasize a potential role for peroxisomes in skeletal muscle lipid metabolism in the obese, insulin-resistant state.
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