Further evidence supporting a potential role for ADH1B in obesity.
Further evidence supporting a potential role for ADH1B in obesity.
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DOI：
10.1038/s41598-020-80563-z
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发表时间：
2021-01-21
影响因子：
4.6
通讯作者：
Jenkinson CP
中科院分区：
文献类型：
--
作者：
Morales LD;Cromack DT;Tripathy D;Fourcaudot M;Kumar S;Curran JE;Carless M;Göring HHH;Hu SL;Lopez-Alvarenga JC;Garske KM;Pajukanta P;Small KS;Glastonbury CA;Das SK;Langefeld C;Hanson RL;Hsueh WC;Norton L;Arya R;Mummidi S;Blangero J;DeFronzo RA;Duggirala R;Jenkinson CP
胰岛素是调节葡萄糖稳态和代谢的重要激素。当组织对胰岛素没有反应时，胰岛素抵抗（IR）就会出现，它会导致严重的健康问题，包括2型糖尿病（T2D）。肥胖是IR和T2D发展的主要因素。我们之前的研究表明，酒精脱氢酶1B （ADH1B）的基因表达与墨西哥裔美国人皮下脂肪组织中的肥胖和IR呈负相关。在目前的研究中，对墨西哥裔美国人、非洲裔美国人、欧洲人和皮马印第安人ADH1B表达与BMI之间关系的荟萃分析证实，BMI随着ADH1B表达的减少而增加。利用来自瘦人（BMI < 30 kg m−2）或肥胖人（BMI≥30 kg m−2）供体的皮下脂肪前细胞系，我们发现ADH1B蛋白在分化过程中表达显著增加，并且ADH1B过表达抑制脂肪酸结合蛋白的表达。来自瘦弱供体的成熟脂肪细胞表达ADH1B的水平高于肥胖供体。胰岛素进一步诱导ADH1B蛋白表达和酶活性。抑制ADH1B表达降低胰岛素刺激的葡萄糖摄取。我们的研究结果表明，ADH1B参与脂肪组织的正常发育和代谢活动，而这种功能被肥胖抑制。
Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with decreased ADH1B expression. Using established human subcutaneous pre-adipocyte cell lines derived from lean (BMI < 30 kg m−2) or obese (BMI ≥ 30 kg m−2) donors, we found that ADH1B protein expression increased substantially during differentiation, and overexpression of ADH1B inhibited fatty acid binding protein expression. Mature adipocytes from lean donors expressed ADH1B at higher levels than obese donors. Insulin further induced ADH1B protein expression as well as enzyme activity. Knockdown of ADH1B expression decreased insulin-stimulated glucose uptake. Our findings suggest that ADH1B is involved in the proper development and metabolic activity of adipose tissues and this function is suppressed by obesity.
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影响因子：
7.7
作者：
Garin-Shkolnik, Tali;Rudich, Assaf;Rubinstein, Menachem
通讯作者：
Rubinstein, Menachem
影响因子：
--
作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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