Loss of TDAG51 results in mature-onset obesity, hepatic steatosis, and insulin resistance by regulating lipogenesis.
Loss of TDAG51 results in mature-onset obesity, hepatic steatosis, and insulin resistance by regulating lipogenesis.
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作者：
Basseri S;Lhoták S;Fullerton MD;Palanivel R;Jiang H;Lynn EG;Ford RJ;Maclean KN;Steinberg GR;Austin RC
调节能量代谢对于预防肥胖、糖尿病和肝脂肪变性至关重要。在这里，我们报告了普列克底物蛋白同源相关域家族成员，T细胞死亡相关基因51（TDAG 51），在调节能量代谢的重要作用。在脂肪细胞分化过程中检测TDAG 51表达。评估TDAG 51敲低或缺失的前脂肪细胞的成脂潜力。体重增加，胰岛素敏感性，代谢率和肝脏脂质含量也在TDAG 51缺陷（TDAG 51-/-）和野生型小鼠之间进行了比较。除了其在肝脏中相对高的表达之外，TDAG 51还存在于白色脂肪组织（WAT）中。TDAG 51在脂肪形成过程中下调，TDAG 51 −/−前脂肪细胞表现出更大的脂肪形成潜力。喂食普通饲料的TDAG 51 −/−小鼠表现出更大的身体和WAT质量，能量消耗减少，表现出成熟型胰岛素抵抗（IR），并易患肝脂肪变性。TDAG 51 −/−小鼠的肝脏甘油三酯和SREBP-1靶基因表达增加。此外，在多种肝脂肪变性小鼠模型中，TDAG 51表达与脂肪肝呈负相关。总之，我们的研究结果表明，TDAG 51至少部分通过调节肝脏和WAT中的脂肪生成参与能量稳态，因此，可能构成治疗肥胖和IR的新治疗靶点。
Regulation of energy metabolism is critical for the prevention of obesity, diabetes, and hepatic steatosis. Here, we report an important role for the pleckstrin homology–related domain family member, T-cell death–associated gene 51 (TDAG51), in the regulation of energy metabolism. TDAG51 expression was examined during adipocyte differentiation. Adipogenic potential of preadipocytes with knockdown or absence of TDAG51 was assessed. Weight gain, insulin sensitivity, metabolic rate, and liver lipid content were also compared between TDAG51-deficient (TDAG51−/−) and wild-type mice. In addition to its relatively high expression in liver, TDAG51 was also present in white adipose tissue (WAT). TDAG51 was downregulated during adipogenesis, and TDAG51−/− preadipocytes exhibited greater lipogenic potential. TDAG51−/− mice fed a chow diet exhibited greater body and WAT mass, had reduced energy expenditure, displayed mature-onset insulin resistance (IR), and were predisposed to hepatic steatosis. TDAG51−/− mice had increased hepatic triglycerides and SREBP-1 target gene expression. Furthermore, TDAG51 expression was inversely correlated with fatty liver in multiple mouse models of hepatic steatosis. Taken together, our findings suggest that TDAG51 is involved in energy homeostasis at least in part by regulating lipogenesis in liver and WAT, and hence, may constitute a novel therapeutic target for the treatment of obesity and IR.
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影响因子：
64.5
作者：
Chakraborty A;Koldobskiy MA;Bello NT;Maxwell M;Potter JJ;Juluri KR;Maag D;Kim S;Huang AS;Dailey MJ;Saleh M;Snowman AM;Moran TH;Mezey E;Snyder SH
通讯作者：
Snyder SH
影响因子：
6.5
作者：
Basseri, Sana;Lhotak, Sarka;Austin, Richard C.
通讯作者：
Austin, Richard C.
DOI：
10.1073/pnas.96.22.12737
发表时间：
1999-10-26
影响因子：
11.1
作者：
Foretz, M;Guichard, C;Foufelle, F
通讯作者：
Foufelle, F
影响因子：
7.7
作者：
Chan CB;Liu X;Jung DY;Jun JY;Luo HR;Kim JK;Ye K
通讯作者：
Ye K
影响因子：
14.8
作者：
Kelley, Lawrence A.;Sternberg, Michael J. E.
通讯作者：
Sternberg, Michael J. E.