血红素生物合成途径通过线粒体呼吸活性与脂肪生成功能相关联。
Heme Biosynthetic Pathway is Functionally Linked to Adipogenesis via Mitochondrial Respiratory Activity.
作者信息
Moreno-Navarrete José María, Rodríguez Amaia, Ortega Francisco, Becerril Sara, Girones Jordi, Sabater-Masdeu Mònica, Latorre Jéssica, Ricart Wifredo, Frühbeck Gema, Fernández-Real José Manuel
机构信息
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III, Girona, Spain.
Metabolic Research Laboratory, Clínica Universidad de Navarra, CIBEROBN, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
出版信息
Obesity (Silver Spring). 2017 Oct;25(10):1723-1733. doi: 10.1002/oby.21956. Epub 2017 Aug 31.
OBJECTIVE
To investigate key enzymes of heme biosynthesis in human adipocytes and adipose tissue (AT).
METHODS
Heme biosynthesis-related gene expression (ALAS1, ALAD, HMBS) was investigated in whole AT from humans (n = 178 and n = 75) and rats according to obesity status and during adipogenesis of human preadipocytes. The effects of aminotriazole (an ALAD inhibitor) and of ALAD knockdown were also studied.
RESULTS
Consistent heme biosynthesis-related gene expression was detected in both subcutaneous AT (SAT) and visceral AT (VAT) and was significantly increased in SAT. ALAS1, ALAD, and HMBS mRNAs were positively associated with adipogenic gene expression in human AT and significantly decreased in subjects with obesity. These results were replicated in an independent cohort. Both SAT and VAT heme levels were positively correlated with ALAS1, ALAD, and HMBS mRNAs. ALAD and HMBS were mainly expressed in adipocytes and increased during differentiation of human adipocytes in parallel to adipogenic genes. In rats, high-fat diet-induced weight gain resulted in decreased Alad and Hmbs mRNAs in a similar way to what was observed with Adipoq. Aminotriazole administration or ALAD knockdown attenuated adipogenesis in parallel with decreased glucose uptake and impaired mitochondrial respiratory function during human adipocyte differentiation.
CONCLUSIONS
Current data suggest a possible role of heme biosynthesis in human adipogenesis.
目的
研究人类脂肪细胞和脂肪组织（AT）中血红素生物合成的关键酶。
方法
根据肥胖状态以及人类前脂肪细胞的脂肪生成过程，研究人类（n = 178和n = 75）和大鼠的全脂肪组织中血红素生物合成相关基因的表达（ALAS1、ALAD、HMBS）。还研究了氨基三唑（一种ALAD抑制剂）和ALAD基因敲低的作用。
结果
在皮下脂肪组织（SAT）和内脏脂肪组织（VAT）中均检测到一致的血红素生物合成相关基因表达，且在SAT中显著增加。ALAS1、ALAD和HMBS mRNA与人类脂肪组织中的脂肪生成基因表达呈正相关，在肥胖受试者中显著降低。这些结果在一个独立队列中得到了重复验证。SAT和VAT的血红素水平均与ALAS1、ALAD和HMBS mRNA呈正相关。ALAD和HMBS主要在脂肪细胞中表达，并在人类脂肪细胞分化过程中与脂肪生成基因平行增加。在大鼠中，高脂饮食诱导的体重增加导致Alad和Hmbs mRNA下降，其方式与Adipoq观察到的相似。在人类脂肪细胞分化过程中，给予氨基三唑或敲低ALAD可减弱脂肪生成，同时葡萄糖摄取减少且线粒体呼吸功能受损。
结论
目前的数据表明血红素生物合成在人类脂肪生成中可能发挥作用。
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