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大量体重减轻揭示了人类皮下和内脏脂肪组织中不同的基因表达变化。

Extensive weight loss reveals distinct gene expression changes in human subcutaneous and visceral adipose tissue.

作者信息

Mardinoglu Adil, Heiker John T, Gärtner Daniel, Björnson Elias, Schön Michael R, Flehmig Gesine, Klöting Nora, Krohn Knut, Fasshauer Mathias, Stumvoll Michael, Nielsen Jens, Blüher Matthias

机构信息

Department of Biology and Biological Engineering, Chalmers University of Technology, SE-412 96, Gothenburg, Sweden.

Science for Life Laboratory, KTH - Royal Institute of Technology, SE-171 21, Stockholm, Sweden.

出版信息

Sci Rep. 2015 Oct 5;5:14841. doi: 10.1038/srep14841.

Abstract

Weight loss has been shown to significantly improve Adipose tissue (AT) function, however changes in AT gene expression profiles particularly in visceral AT (VAT) have not been systematically studied. Here, we tested the hypothesis that extensive weight loss in response to bariatric surgery (BS) causes AT gene expression changes, which may affect energy and lipid metabolism, inflammation and secretory function of AT. We assessed gene expression changes by whole genome expression chips in AT samples obtained from six morbidly obese individuals, who underwent a two step BS strategy with sleeve gastrectomy as initial and a Roux-en-Y gastric bypass as second step surgery after 12 ± 2 months. Global gene expression differences in VAT and subcutaneous (S)AT were analyzed through the use of genome-scale metabolic model (GEM) for adipocytes. Significantly altered gene expressions were PCR-validated in 16 individuals, which also underwent a two-step surgery intervention. We found increased expression of cell death-inducing DFFA-like effector a (CIDEA), involved in formation of lipid droplets in both fat depots in response to significant weight loss. We observed that expression of the genes associated with metabolic reactions involved in NAD+, glutathione and branched chain amino acid metabolism are significantly increased in AT depots after surgery-induced weight loss.

摘要

体重减轻已被证明能显著改善脂肪组织(AT)的功能,然而,AT基因表达谱的变化,尤其是内脏脂肪组织(VAT)的变化尚未得到系统研究。在此,我们验证了一个假设,即减肥手术(BS)导致的大量体重减轻会引起AT基因表达变化,这可能会影响AT的能量和脂质代谢、炎症及分泌功能。我们通过全基因组表达芯片评估了从六名病态肥胖个体获取的AT样本中的基因表达变化,这些个体接受了两步减肥手术策略,第一步是袖状胃切除术,12±2个月后第二步是Roux-en-Y胃旁路手术。通过使用脂肪细胞的基因组规模代谢模型(GEM)分析了VAT和皮下脂肪组织(SAT)中的全局基因表达差异。对另外16名同样接受了两步手术干预的个体,通过PCR验证了显著改变的基因表达。我们发现,在显著体重减轻后,参与两个脂肪库中脂滴形成的细胞死亡诱导DFFA样效应因子a(CIDEA)的表达增加。我们观察到,手术引起体重减轻后,AT库中与NAD +、谷胱甘肽和支链氨基酸代谢相关的代谢反应基因表达显著增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e20/4593186/d7289d7e82cf/srep14841-f1.jpg

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