Department of Diabetes, Endocrinology and Nutrition Institut d'Investigació Biomèdica de Girona (IdIBGi), CIBEROBN (CB06/03/010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
NeurObesity Group, Department of Physiology, CiMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain & CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, 15706, Spain.
Int J Obes (Lond). 2019 Aug;43(8):1611-1619. doi: 10.1038/s41366-018-0203-1. Epub 2018 Sep 11.
BACKGROUND/OBJECTIVES: Recent studies indicate a possible role of TSH/TSHR signalling axis on adipogenesis and adipose tissue physiology. Here, we aimed to investigate the relationship between adipose tissue TSHB and adipose tissue physiology-related gene expression.
SUBJECTS/METHODS: Subcutaneous and visceral adipose tissue TSHB gene expression was analysed in two independent cohorts [Cohort1 (N = 96) and Cohort2 (N = 45)] and after bariatric surgery-induced weight loss [Cohort3 (N = 22)]. Adipose tissue TSH protein expression was also analysed in a subgroup of participants from Cohort 1 (N = 16). The effects of recombinant TSH on human subcutaneous preadipocytes and adipocytes were investigated.
In cohort 1, both visceral and subcutaneous adipose tissue TSHB gene expression was positively correlated with the expression of mitochondrial function (PPARGC1A, ISCA2, CISD1, SIRT1, NFE2L2, NRF1) and fatty acid mobilization (CAV1, ENGL1), but not with adipogenic-related genes. Of note, adipose tissue TSH protein levels were also associated with some of these markers of mitochondrial function and fatty acid mobilization. These associations were replicated in cohort 2. Bariatric surgery-induced weight loss resulted in increased subcutaneous adipose tissue TSHB in parallel to increased PPARGC1A. In human subcutaneous adipocytes, rh-TSH administration led to increased mitochondrial respiratory capacity in parallel to increased mitochondrial function- and adipogenic-related gene expression, but no significant effects were observed during differentiation of human preadipocytes.
These data point to a possible role of adipose tissue TSH in the maintenance of adipocyte mitochondrial function.
背景/目的：最近的研究表明 TSH/TSHR 信号轴可能在脂肪生成和脂肪组织生理学中发挥作用。在这里，我们旨在研究脂肪组织 TSHB 与脂肪组织生理学相关基因表达之间的关系。
受试者/方法：在两个独立队列[队列 1（N=96）和队列 2（N=45）]和减肥手术后[队列 3（N=22）]分析了皮下和内脏脂肪组织 TSHB 基因表达。还分析了来自队列 1 的一部分参与者的脂肪组织 TSH 蛋白表达（N=16）。研究了重组 TSH 对人皮下前体脂肪细胞和脂肪细胞的影响。
在队列 1 中，内脏和皮下脂肪组织 TSHB 基因表达均与线粒体功能（PPARGC1A、ISCA2、CISD1、SIRT1、NFE2L2、NRF1）和脂肪酸动员（CAV1、ENGL1）的表达呈正相关，但与脂肪生成相关基因无关。值得注意的是，脂肪组织 TSH 蛋白水平也与这些线粒体功能和脂肪酸动员标志物中的一些相关。这些关联在队列 2 中得到了复制。减肥手术后，皮下脂肪组织 TSHB 增加，同时 PPARGC1A 增加。在人类皮下脂肪细胞中，rh-TSH 给药导致线粒体呼吸能力增加，同时线粒体功能和脂肪生成相关基因表达增加，但在人类前体脂肪细胞分化过程中没有观察到明显的作用。
这些数据表明脂肪组织 TSH 可能在维持脂肪细胞线粒体功能方面发挥作用。
