miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset

被引:41
作者
Sanchez-Ceinos, Julia [1 ,2 ]
Rangel-Zuniga, Oriol A. [2 ,3 ]
Clemente-Postigo, Mercedes [1 ]
Podadera-Herreros, Alicia [1 ,2 ]
Camargo, Antonio [2 ,3 ]
Francisco Alcala-Diaz, Juan [2 ,3 ]
Guzman-Ruiz, Rocio [1 ,2 ]
Lopez-Miranda, Jose [2 ,3 ]
Malagon, Maria M. [1 ,2 ]
机构
[1] Univ Cordoba, Dept Cell Biol Physiol & Immunol, Reina Sofia Univ Hosp, Maimonides Biomed Res Inst Cordoba IMIBIC, Avda Menendez Pidal S-N, Cordoba 14004, Spain
[2] Inst Salud Carlos III ISCIII, CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Madrid 28029, Spain
[3] Univ Cordoba, Lipids & Atherosclerosis Unit, Dept Internal Med, IMIBIC,Reina Sofia Univ Hosp, Avda Menendez Pidal S-N, Cordoba 14004, Spain
关键词
INSULIN-RESISTANCE; CIRCULATING MIRNAS; OXIDATIVE STRESS; GLUCOSE-UPTAKE; OBESITY; ADIPOCYTES; EXPRESSION; MICRORNAS; INTERVENTION; ACTIVATION;
D O I
10.1016/j.omtn.2021.01.014
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Circulating microRNAs (miRNAs) have been proposed as biomarkers for type 2 diabetes (T2D). Adipose tissue (AT), for which dysfunction is widely associated with T2D development, has been reported as a major source of circulating miRNAs. However, the role of dysfunctional AT in the altered pattern of circulating miRNAs associated with T2D onset remains unexplored. Herein, we investigated the relationship between T2D-associated circulating miRNAs and AT function, as well as the role of preadipocytes and adipocytes as secreting cells of candidate circulating miRNAs. Among the plasma miRNAs related to T2D onset in the CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) cohort, baseline miR-223-3p levels (diminished in patients who next developed T2D [incident-T2D]) were significantly related to AT insulin resistance (IR). Baseline serum from incident-T2D participants induced inflammation and IR in 3T3-L1 adipocytes. We demonstrated that tumor necrosis factor (TNF)-alpha inhibited miR-223-3p secretion while enhancing miR-223-3p intracellular accumulation in 3T3-L1 (pre)adipocytes. Overexpression studies showed that an intracellular increase of miR-223-3p impaired glucose and lipid metabolism in these cells. Our findings provide mechanistic insights into the alteration of circulating miRNAs preceding T2D, unveiling both preadipocytes and adipocytes as miR-223-3p-secreting cells and suggesting that inflammation promotes miR-223-3p intracellular accumulation, which might contribute to (pre)adipocyte dysfunction and body metabolic dysregulation.
引用
收藏
页码:1035 / 1052
页数:18
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