کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1905836 1534743 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Functioning of oxidative phosphorylation in liver mitochondria of high-fat diet fed rats
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Functioning of oxidative phosphorylation in liver mitochondria of high-fat diet fed rats
چکیده انگلیسی

We proposed that inhibition of mitochondrial adenine nucleotide translocator (ANT) by long chain acyl-CoA (LCAC) underlies the mechanism associating obesity and type 2 diabetes. Here we test that after long-term exposure to a high-fat diet (HFD): (i) there is no adaptation of the mitochondrial compartment that would hinder such ANT inhibition, and (ii) ANT has significant control of the relevant aspects of oxidative phosphorylation. After 7 weeks, HFD induced a 24 ± 6% increase in hepatic LCAC concentration and accumulation of the oxidative stress marker Nε-(carboxymethyl)lysine. HFD did not significantly affect mitochondrial copy number, oxygen uptake, membrane potential (Δψ), ADP/O ratio, and the content of coenzyme Q9, cytochromes b and a + a3. Modular kinetic analysis showed that the kinetics of substrate oxidation, phosphorylation, proton leak, ATP-production and ATP-consumption were not influenced significantly. After HFD-feeding ANT exerted considerable control over oxygen uptake (control coefficient C = 0.14) and phosphorylation fluxes (C = 0.15), extra- (C = 0.23) and intramitochondrial (C = − 0.56) ATP/ADP ratios, and Δψ (C = − 0.11). We conclude that although HFD induces accumulation of LCAC and Nε-(carboxymethyl)lysine, oxidative phosphorylation does not adapt to these metabolic challenges. Furthermore, ANT retains control of fluxes and intermediates, making inhibition of this enzyme a more probable link between obesity and type 2 diabetes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1772, Issue 3, March 2007, Pages 307–316
نویسندگان
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