Changes in Peroxisomal Fatty Acid Oxidation in the Diabetic Rat Liver

Horie, Seichi; Ishii, Hidemi; Suga, Tetsuya

doi:10.1093/oxfordjournals.jbchem.a133645

Cited by 151 publications

(68 citation statements)

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“…8B). Figure 8A shows that catalase activity was virtually undetectable in skeletal muscle fractions and that CS activity was highest in fractions [11][12][13][14][15][16]. Fractions 13-15 (highlighted within a box) were combined and used as the isolated/ purified mitochondrial fraction for subsequent oxidation studies.…”

Section: Organelle Intactness Assay Results Presented Inmentioning

confidence: 99%

Peroxisomal-mitochondrial oxidation in a rodent model of obesity-associated insulin resistance

Noland¹,

Woodlief²,

Whitfield³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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Noland RC, Woodlief TL, Whitfield BR, Manning SM, Evans JR, Dudek RW, Lust RM, Cortright RN. Peroxisomal-mitochondrial oxidation in a rodent model of obesity-associated insulin resistance. Am J Physiol Endocrinol Metab 293: E986-E1001, 2007. First published July 17, 2007; doi:10.1152/ajpendo.00399.2006.-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 (CO2 production) using various lipid substrates was increased approximately twofold in MG, unaltered in LV, and diminished ϳ50% in liver of fa/fa rats. In isolated mitochondria, malonyl-CoA inhibited CO2 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 CO2 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. fatty acid; lipid metabolism; liver; heart; skeletal muscle; Zucker rat EXCESS LIPID ACCUMULATION is implicated in the pathophysiology of obesity-associated insulin resistance, and many believe this is secondary to impairments in lipid disposal pathways (22,38,48,52,55,56). Consequently, much research has focused on primary aspects involved in lipid metabolism, such as mitochondrial oxidative capacity, lipid transport, and lipid trafficking. However, an important factor that has largely been overlooked with respect to maintaining a healthy cellular lipid environment is the peroxisome. Peroxisomes are ubiquitously expressed and have a wide range of cellular functions, including a primary role in fatty acid oxidation (68). Unlike mitochondria, peroxisomal ␤-oxidation is incomplete and cannot chain-shorten fatty acids beyond six carbon residues (50), thus leaving a medium-chain acyl-CoA derivative as well as acetylCoA residues. Since peroxisomes lack a tricarboxylic acid cycle and electron transport system, the products of peroxisomal oxidation are not linked di...

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Section: Organelle Intactness Assay Results Presented Inmentioning

confidence: 99%

Peroxisomal-mitochondrial oxidation in a rodent model of obesity-associated insulin resistance

Noland¹,

Woodlief²,

Whitfield³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…Numerous CoA thioesters are also involved in the post-translational modification of histones and thousands of other proteins (1)(2)(3)(4)(5). Three major subcellular CoA pools are found in the cytosol, mitochondria, and peroxisomes to support specific metabolic pathways (6,7). These include, among others, fatty acid synthesis in the cytosol, the TCA cycle and oxidation of longchain and medium-chain fatty acids in the mitochondria, and bile acid conjugation and oxidation of very long-chain and branched-chain fatty acids in the peroxisomes.…”

Section: Introductionmentioning

confidence: 99%

Nudt19 is a renal CoA diphosphohydrolase with biochemical and regulatory properties that are distinct from the hepatic Nudt7 isoform

Shumar

Kerr

Geldenhuys

et al. 2018

Journal of Biological Chemistry

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“…ß-oxidation of fatty acids initiated by increased activity of enzyme fatty acyl coenzyme A oxidase due to hypoinsulinemia results lipid peroxidation [52]. The products of lipid peroxidation such as MDA are harmful to most of body cells and are associated different disease conditions such as brain damage, micro-and macrovascular complications [53].…”

Section: Discussionmentioning

confidence: 99%