Koh Eun Hee, Park Joong-Yeol, Park Hye-Sun, Jeon Min Jae, Ryu Je Won, Kim Mina, Kim Sun Young, Kim Min-Seon, Kim Seung-Whan, Park In Sun, Youn Jang Hyun, Lee Ki-Up
Department of Internal Medicine, University of Ulsan College of Medicine, Poongnap-dong, Songpa-ku, Seoul 138-736, Korea.
Diabetes. 2007 Dec;56(12):2973-81. doi: 10.2337/db07-0510. Epub 2007 Sep 7.
Adiponectin is an important adipocytokine that improves insulin action and reduces atherosclerotic processes. The plasma adiponectin level is paradoxically reduced in obese individuals, but the underlying mechanism is unknown. This study was undertaken to test the hypothesis that mitochondrial function is linked to adiponectin synthesis in adipocytes.
We examined the effects of rosiglitazone and the measures that increase or decrease mitochondrial function on adiponectin synthesis. We also examined the molecular mechanism by which changes in mitochondrial function affect adiponectin synthesis.
Adiponectin expression and mitochondrial content in adipose tissue were reduced in obese db/db mice, and these changes were reversed by the administration of rosiglitazone. In cultured adipocytes, induction of increased mitochondrial biogenesis (via adenoviral overexpression of nuclear respiratory factor-1) increased adiponectin synthesis, whereas impairment in mitochondrial function decreased it. Impaired mitochondrial function increased endoplasmic reticulum (ER) stress, and agents causing mitochondrial or ER stress reduced adiponectin transcription via activation of c-Jun NH(2)-terminal kinase (JNK) and consequent induction of activating transcription factor (ATF)3. Increased mitochondrial biogenesis reversed all of these changes.
Mitochondrial function is linked to adiponectin synthesis in adipocytes, and mitochondrial dysfunction in adipose tissue may explain decreased plasma adiponectin levels in obesity. Impaired mitochondrial function activates a series of mechanisms involving ER stress, JNK, and ATF3 to decrease adiponectin synthesis.
脂联素是一种重要的脂肪细胞因子，可改善胰岛素作用并减少动脉粥样硬化进程。肥胖个体的血浆脂联素水平反而降低，但其潜在机制尚不清楚。本研究旨在验证线粒体功能与脂肪细胞中脂联素合成相关的假说。
我们研究了罗格列酮以及增加或降低线粒体功能的措施对脂联素合成的影响。我们还研究了线粒体功能变化影响脂联素合成的分子机制。
肥胖的db/db小鼠脂肪组织中的脂联素表达和线粒体含量降低，而罗格列酮给药可逆转这些变化。在培养的脂肪细胞中，增加线粒体生物发生（通过核呼吸因子-1的腺病毒过表达）可增加脂联素合成，而线粒体功能受损则会降低其合成。线粒体功能受损会增加内质网（ER）应激，导致线粒体或ER应激的药物通过激活c-Jun NH(2)-末端激酶（JNK）并随后诱导激活转录因子（ATF）3来降低脂联素转录。增加线粒体生物发生可逆转所有这些变化。
线粒体功能与脂肪细胞中脂联素合成相关，脂肪组织中的线粒体功能障碍可能解释肥胖患者血浆脂联素水平降低的原因。线粒体功能受损会激活一系列涉及ER应激、JNK和ATF3的机制，从而降低脂联素合成。
