Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice
Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice
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DOI：
10.1172/jci44271
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发表时间：
2011-01-01
影响因子：
15.9
通讯作者：
Spiegelman, Bruce M.
中科院分区：
文献类型：
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作者：
Seale, Patrick;Conroe, Heather M.;Spiegelman, Bruce M.
在啮齿类动物和人类中，过多的腹部脂肪是代谢性疾病的主要危险因素，而皮下脂肪的扩张不具有同样的风险。棕色脂肪产生热量，作为对低温和肥胖的防御，白色脂肪组织库中棕色样脂肪细胞的出现与代谢表型的改善有关。了解这些不同脂肪细胞类型和储存的细胞生物学和功能的差异可能对开发代谢疾病的新疗法至关重要。在这里，我们发现Prdm16，一种棕色脂肪决定因子，在小鼠皮下白色脂肪细胞中选择性表达，相对于其他白色脂肪储存，在脂肪组织中转基因表达Prdm16强烈诱导皮下棕色脂肪细胞的发育，而不是附睾。脂肪库Prdm16转基因小鼠对高脂肪饮食的反应显示出能量消耗增加，体重增加有限，葡萄糖耐量改善，shrna介导的分离皮下脂肪细胞中Prdm16的消耗导致产热基因的表达急剧下降，非偶联细胞呼吸减少。这些结果表明，Prdm16是皮下脂肪组织中棕色脂肪样基因程序和产热作用的细胞自主决定因素
The white adipose organ is composed of both subcutaneous and several intra-abdominal depots Excess abdominal adiposity is a major risk factor for metabolic disease in rodents and humans, while expansion of subcutaneous fat does not carry the same risks Brown adipose produces heat as a defense against hypothermia and obesity, and the appearance of brown-like adipocytes within white adipose tissue depots is associated with improved metabolic phenotypes Thus, understanding the differences in cell biology and function of these different adipose cell types and depots may be critical to the development of new therapies for metabolic disease Here, we found that Prdm16, a brown adipose determination factor, is selectively expressed in subcutaneous white adipocytes relative to other white fat depots in mice Transgenic expression of Prdm16 in fat tissue robustly induced the development of brown-like adipocytes in subcutaneous, but not epididymal, adipose depots Prdm16 transgenic mice displayed increased energy expenditure, limited weight gain, and improved glucose tolerance in response to a high-fat diet shRNA-mediated depletion of Prdm16 in isolated subcutaneous adipocytes caused a sharp decrease in the expression of thermogenic genes and a reduction in uncoupled cellular respiration Finally, Prdm16 haploinsufficiency reduced the brown fat phenotype in white adipose tissue stimulated by beta-adrenergic agonists These results demonstrate that Prdm16 is a cell-autonomous determinant of a brown fat-like gene program and thermogenesis in subcutaneous adipose tissues