Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro
Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro
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DOI：
10.1210/jc.2005-1024
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发表时间：
2005-12-01
影响因子：
5.8
通讯作者：
Smith, SR
中科院分区：
文献类型：
--
作者：
Bogacka, I;Ukropcova, B;Smith, SR
简介：线粒体生物合成是一个复杂的过程，在肌肉或棕色脂肪细胞中，有几种因子和信号通路调节这一过程。本研究的目的是探讨影响线粒体生物合成和脂肪酸氧化（FAO）在人白色脂肪cytes.Methods：人前脂肪细胞从吸脂标本在体外分化的途径。在分化的第10天，向培养基中加入4 μ M毛喉素和1 μ M过氧化物酶体增殖物激活受体-γ（PPAR-gamma）激动剂（吡格列酮、罗格列酮或GW 929）或10 μ M（PPAR-gamma）激动剂（WY-14，643）96小时。使用定量实时PCR来确定基因表达/线粒体拷贝数，并使用C-14标记的棕榈酸酯来测量直接能量耗散。用毛喉素处理脂肪细胞增加了线粒体拷贝数和参与线粒体生物合成的基因（PPAR γ共激活因子1 α和转录因子A）和脂肪酸氧化（PPAR α和中链酰基辅酶A脱氢酶）的表达。毛喉素处理后，FAO的最终产物（CO2）和中间产物（C-14标记的酸溶性产物）也有所增加。PPAR γ和PPAR α激动剂增加线粒体拷贝数、解偶联蛋白1、中链酰基辅酶A脱氢酶和肉毒碱棕榈酰转移酶1，但不改变PPAR α、PPAR γ辅激活因子1 α或转录因子A mRNA水平。FAO在罗格列酮、GW 929和WY-14，643后较高，但在吡格列酮治疗后不高。结论：cAMP或PPAR γ通路的药理学激活将白色脂肪细胞推向氧化连续体。直接的能量耗散效应可能是治疗肥胖和通过减少脂肪细胞中的脂肪积累或通过重编程脂肪酸代谢来改善2型糖尿病患者的胰岛素抵抗的重要工具。
Introduction: Mitochondrial biogenesis is a complex process, and several factors and signaling pathways regulate this process in muscle or brown adipocytes. The aim of the study was to explore pathways affecting mitochondrial biogenesis and fatty acid oxidation ( FAO) in human white adipocytes.Methods: Human preadipocytes obtained from liposuction samples were differentiated in vitro. On the 10th day of differentiation, 4 mu M forskolin and 1 mu M peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist ( pioglitazone, rosiglitazone, or GW 929) or 10 mu M (PPAR gamma) agonist (WY-14,643) were added to the media for 96 h. Quantitative real-time PCR was used to determine gene expression/mitochondrial copy number and C-14- labeled palmitate to measure direct energy dissipation.Results: The treatment of adipocytes with forskolin increased mitochondrial copy number and the expression of genes involved in mitochondrial biogenesis ( PPAR gamma coactivator 1 alpha and transcriptional factor A) and fatty acid oxidation ( PPAR alpha and medium-chain acylcoenzyme A dehydrogenase). The end ( CO2) and intermediate products ( C-14- labeled acid-soluble products) of FAO were also increased after forskolin treatment. PPAR gamma and PPAR alpha agonists increased mitochondrial copy number, uncoupling protein 1, medium-chain acylcoenzyme Adehydrogenase, and carnitine palmitoyltransferase 1, but did not change PPAR alpha, PPAR gamma coactivator 1 alpha, or transcriptional factor A mRNA levels. FAO was higher after rosiglitazone, GW 929, and WY-14,643 but not after pioglitazone treatment.Conclusions: Pharmacological activation of the cAMP or PPAR gamma pathway pushes the white adipocyte down the oxidative continuum. The direct energy-dissipating effects could be significant tools to treat obesity and to improve insulin resistance in type 2 diabetic patients by reduction of fat accumulation in adipocytes or by reprogramming fatty acid metabolism.