Noland Robert C, Woodlief Tracey L, Whitfield Brian R, Manning Steven M, Evans Jasper R, Dudek Ronald W, Lust Robert M, Cortright Ronald N
Department of Physiology, East Carolina University, Greenville, NC 27858, USA.
Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E986-E1001. doi: 10.1152/ajpendo.00399.2006. Epub 2007 Jul 17.
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.
过氧化物酶体氧化产生的代谢产物能被线粒体更有效地利用。这具有潜在的临床重要性，因为脂肪酸氧化减少被怀疑会促进肥胖相关胰岛素抵抗中脂质的过度积累。我们的目的是评估过氧化物酶体对来自瘦型和肥胖型（fa/fa） Zucker大鼠的混合腓肠肌（MG）、肝脏和左心室（LV）匀浆中线粒体氧化的贡献。结果表明，使用各种脂质底物时，完全线粒体氧化（二氧化碳产生量）在MG中增加了约两倍，在LV中未改变，而在fa/fa大鼠的肝脏中减少了约50%。在分离的线粒体中，丙二酰辅酶A抑制棕榈酸产生二氧化碳的能力达78%，而添加分离的过氧化物酶体可将抑制作用降低至21%。这些数据表明，过氧化物酶体产物可能独立于肉碱棕榈酰转移酶I进入线粒体，从而在丙二酰辅酶A水平升高的情况下（如在胰岛素抵抗组织中）提供一条维持脂质处理的途径。fa/fa大鼠中二十四烷酸的过氧化物酶体代谢在肝脏和MG中均升高（LV未改变），但过氧化物酶体产物分布有所不同。不完全氧化增加三倍是肝脏过氧化物酶体氧化增加（二氧化碳产生量未改变）的唯一原因。相反，在MG中仅检测到二氧化碳，表明过氧化物酶体产物专门分配到线粒体进行完全脂质处理。这些数据表明过氧化物酶体衍生产物的组织特异性归宿，并强调过氧化物酶体在肥胖、胰岛素抵抗状态下骨骼肌脂质代谢中的潜在作用。
