Association of Lifestyle-Induced Weight Loss With Gene Expression in Subcutaneous Adipose Tissue in Metabolic Syndrome

IF 3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Silke Zimmermann, Kirsten Roomp, Hans-Jonas Meyer, Akash Mathew, Manuel Florian Struck, Matthias Blüher, Hugo N. G. Martin, Maria Keller, Kathrin Landgraf, Antje Körner, Anne Hoffmann, Yvonne Böttcher, Kathleen Biemann, Adhideb Ghosh, Christian Wolfrum, Falko Noé, Berend Isermann, Jochen G. Schneider, Ronald Biemann
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引用次数: 0

Abstract

Aims

Lifestyle-induced weight loss (LIWL) is considered an effective therapy for the treatment of metabolic syndrome (MetS). The role of differentially expressed genes (DEGs) in adipose tissue function and in the success of LIWL in MetS is still unclear. We investigated the effect of 6 months of LIWL on transcriptional regulation in subcutaneous adipose tissue (SAT). Aiming to identify a LIWL-associated “gene signature” in SAT, DEGs were fitted into a linear regression model.

Materials and Methods

The study is embedded in a prospective, two-arm, controlled, monocentric, randomized, 6-month interventional trial in individuals with MetS following LIWL. The trial included 43 nonsmoking, nondiabetic men aged 45–55 years with MetS.

Results

In total, we identified 642 DEGs in SAT after 6 months of LIWL. The identified DEGs were validated in two cross-sectional cohorts analyzing SAT from individuals with and without obesity. Gene enrichment analysis of the DEGs revealed the strongest association with cholesterol metabolic processes. Accordingly, DEGs were correlated with the lipid parameters HDL cholesterol, LDL cholesterol, and triglycerides in corresponding serum samples. We identified 3 genes with an AUC of 0.963 (95% CI: 0.906–1.0) associated with a loss of more than 10% of initial body weight that was maintained for at least 12 months after LIWL, namely SUMO3 (Small ubiquitin-related modifier 3), PRKG2 (Protein Kinase CGMP-Dependent 2), and ADAP2 (ArfGAP with Dual PH Domains 2).

Conclusion

In summary, we have identified DEGs in SAT after LIWL, which may play an important role in metabolic functions. In particular, altered gene expression in SAT may predict sustained weight loss.

Abstract Image

生活方式引起的体重减轻与代谢综合征患者皮下脂肪组织基因表达的关系
目的生活方式诱导减肥(LIWL)被认为是治疗代谢综合征(MetS)的有效方法。差异表达基因(DEGs)在脂肪组织功能中的作用以及在MetS中LIWL成功的作用尚不清楚。我们研究了6个月LIWL对皮下脂肪组织(SAT)转录调节的影响。为了确定SAT中与liwl相关的“基因特征”,deg被拟合到线性回归模型中。材料和方法本研究是一项前瞻性、双臂、对照、单中心、随机、为期6个月的介入试验,研究对象是LIWL后met患者。该试验包括43名年龄在45-55岁之间的非吸烟、非糖尿病的met患者。结果在LIWL 6个月后,我们在SAT中发现了642个deg。确定的deg在两个横断面队列中得到验证,该队列分析了肥胖和非肥胖个体的SAT。基因富集分析显示,deg与胆固醇代谢过程密切相关。因此,deg与相应血清样品中的脂质参数HDL胆固醇、LDL胆固醇和甘油三酯相关。我们鉴定出3个AUC为0.963的基因(95% CI:0.906-1.0)与LIWL后维持至少12个月的初始体重损失超过10%相关,即SUMO3(小泛素相关修饰因子3),PRKG2(蛋白激酶cgmp依赖性2)和ADAP2(双PH域ArfGAP 2)。结论综上所述,我们在LIWL后的SAT中发现了可能在代谢功能中发挥重要作用的DEGs。特别是,SAT基因表达的改变可以预测持续的体重减轻。
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来源期刊
Journal of Diabetes
Journal of Diabetes ENDOCRINOLOGY & METABOLISM-
CiteScore
6.50
自引率
2.20%
发文量
94
审稿时长
>12 weeks
期刊介绍: Journal of Diabetes (JDB) devotes itself to diabetes research, therapeutics, and education. It aims to involve researchers and practitioners in a dialogue between East and West via all aspects of epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes, including the molecular, biochemical, and physiological aspects of diabetes. The Editorial team is international with a unique mix of Asian and Western participation. The Editors welcome submissions in form of original research articles, images, novel case reports and correspondence, and will solicit reviews, point-counterpoint, commentaries, editorials, news highlights, and educational content.
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