Expression of DGAT2 in White Adipose Tissue Is Regulated by Central Leptin Action*
Expression of DGAT2 in White Adipose Tissue Is Regulated by Central Leptin Action*
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DOI：
10.1074/jbc.m410955200
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发表时间：
2005-02
影响因子：
4.8
通讯作者：
R. Suzuki;K. Tobe;M. Aoyama;K. Sakamoto;M. Ohsugi;Nozomu Kamei;S. Nemoto;Atsushi Inoue;Yusuke Ito;Shoko Uchida;K. Hara;T. Yamauchi;N. Kubota;Y. Terauchi;T. Kadowaki
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文献类型：
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作者：
R. Suzuki;K. Tobe;M. Aoyama;K. Sakamoto;M. Ohsugi;Nozomu Kamei;S. Nemoto;Atsushi Inoue;Yusuke Ito;Shoko Uchida;K. Hara;T. Yamauchi;N. Kubota;Y. Terauchi;T. Kadowaki
酰基-CoA：二酰基甘油酰基转移酶（DGAT）酶催化哺乳动物甘油三酯合成的最后一步，并且它们的功能被认为涉及肥胖、胰岛素抵抗和瘦素抵抗的机制。胰岛素受体底物-2（IRS-2）缺陷小鼠表现出肥胖相关的肥大脂肪细胞和瘦素抵抗。筛选脂肪酸和甘油三酯合成相关基因转录本，研究Irs 2-/-小鼠白色脂肪组织（WAT）中DGAT 2 mRNA表达上调，DGAT 1 mRNA表达下调。在瘦素缺陷型ob/ob小鼠的WAT中也观察到DGAT 1和DGAT 2的这种相互表达。高脂饮食也导致C57 BL/6小鼠WAT中DGAT 2增加和DGAT 1减少。体外诱导脂肪细胞肥大可上调3 T3-L1细胞中DGAT 1和DGAT 2的表达，表明DGAT 1和DGAT 2表达的相互变化需要体内脂肪细胞非自主机制。事实上，脑室注射瘦素可降低Irs 2-/-小鼠和ob/ob小鼠WAT中DGAT 2的表达，而与DGAT 1的表达无关。我们提出了这样的假设：瘦素通过中枢神经系统改变DGAT的表达模式来决定甘油三酯的合成水平，从而调节脂肪细胞的大小。
Acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes catalyze the final step in mammalian triglyceride synthesis, and their functions are considered to be involved in the mechanisms of obesity, insulin resistance, and leptin resistance. Insulin receptor substrate-2 (IRS-2)-deficient mice exhibit obesity-associated with hypertrophic adipocytes and leptin resistance. Screening for transcripts of genes involved in fatty acid and triglyceride synthesis to investigate the mechanism of the hypertrophic change in the adipocytes showed that expression of DGAT2 mRNA was up-regulated in the white adipose tissue (WAT) of Irs2–/– mice, whereas that of DGAT1 was down-regulated. This reciprocal expression of DGAT1 and DGAT2 was also observed in WAT of leptin-deficient ob/ob mice. A high fat diet also resulted in increased DGAT2 and reduced DGAT1 in the WAT of C57BL/6 mice. Induction of adipocyte hypertrophy in vitro up-regulated both DGAT1 and DGAT2 expression in 3T3-L1 cells, suggesting that adipocyte non-autonomous mechanism in vivo is required for the reciprocal changes in expression of DGAT1 and DGAT2. In fact, intracerebroventricular infusion of leptin reduced DGAT2 expression in WAT of Irs2–/– mice and ob/ob mice, independently of DGAT1 expression. We propose the hypothesis that leptin regulates adipocyte size by altering expression patterns of DGAT via central nervous system to determine the levels of triglyceride synthesis.