Aging Is Associated With a Shift of Fatty Metabolism Toward Lipogenesis
Aging Is Associated With a Shift of Fatty Metabolism Toward Lipogenesis
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DOI：
10.1093/gerona/glr124
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发表时间：
2011-11-01
影响因子：
5.1
通讯作者：
Vollmar, Brigitte
中科院分区：
文献类型：
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作者：
Kuhla, Angela;Blei, Tina;Vollmar, Brigitte
非酒精性脂肪肝的发病率在老年人群中稳步上升。脂质代谢受核受体维甲酸受体α、肝-X-受体α和过氧化物酶体增殖物激活受体α及其靶基因ABCA 1、固醇调节元件结合蛋白-1c和脂肪酸合酶的转录控制。使用衰老加速倾向小鼠（SAMP 8），我们解决了这个问题，是否与年龄相关的氧化应激增加影响核受体基因表达。与SAMR 1对照小鼠相比，年幼的SAMP 8小鼠表现出肝脂肪变性，肝胆固醇含量、血浆甘油三酯和天冬氨酸转氨酶水平增加。这是伴随着增加的肝-X-受体α和维甲酸受体α的表达，而过氧化物酶体增殖物激活受体α的表达被发现减少。SAMP 8小鼠进一步揭示了ABCA 1以及固醇调节元件结合蛋白-1c的较低表达和脂肪酸合成酶的较高表达。核受体与其靶基因之间的失衡最有可能介导肝脂肪变性，并强调了老年患者脂肪代谢中核受体向脂肪生成转变的病理相关性。
The incidence of nonalcoholic fatty liver disease is steadily increasing among the elderly population. Lipid metabolism is transcriptionally controlled by the nuclear receptors retinoid acid receptor alpha, liver-X-receptor alpha, and peroxisome proliferator-activated receptor alpha and their target genes ABCA1, sterol regulatory element-binding protein-1c, and fatty acid synthase. Using senescence-accelerated prone mice (SAMP8), we addressed the question as to whether age-related increase of oxidative stress affects nuclear receptor gene expression. In contrast to SAMR1 control mice, young SAMP8 mice exhibit hepatic steatosis with increased hepatic cholesterol content, plasma triglyceride, and aspartate aminotransferase levels. This is accompanied by an increase of liver-X-receptor alpha and retinoid acid receptor alpha expression, whereas peroxisome proliferator-activated receptor alpha expression is found diminished. SAMP8 mice further reveal a lower expression of ABCA1 as well as of sterol regulatory element-binding protein-1c and higher expression of fatty acid synthase. The dysbalance between the nuclear receptors and their target genes most probably mediates hepatic steatosis and underlines the pathological relevance of nuclear receptor shift toward lipogenesis in fat metabolism of the elderly patient.