Suppression of GATA-3 increases adipogenesis, reduces inflammation and improves insulin sensitivity in 3T3L-1 preadipocytes

被引：19

作者：

Al-Mansoori, Layla ^{[1
]}

Al-Jaber, Hend ^{[1
]}

Madani, Aisha Y. ^{[2
,3
,4
]}

Mazloum, Nayef A. ^{[3
,4
]}

Agouni, Abdelali ^{[5
]}

Ramanjaneya, Manjunath ^{[6
]}

Abou-Samra, Abdul-Badi ^{[6
]}

Elrayess, Mohamed A. ^{[1
]}

机构：

[1] Qatar Univ, Biomed Res Ctr BRC, Doha, Qatar

[2] Hamad Bin Khalifa Univ HBKU, Qatar Fdn, Coll Hlth & Life Sci, POB 34110, Doha, Qatar

[3] Qatar Fdn, Dept Microbiol, Weill Cornell Med Qatar WCM Q, POB 24144, Doha, Qatar

[4] Qatar Fdn, Dept Immunol, Weill Cornell Med Qatar WCM Q, POB 24144, Doha, Qatar

[5] Qatar Univ, Coll Pharm, Dept Pharmaceut Sci, QU Hlth, Doha, Qatar

[6] Hamad Med Corp, Qatar Metab Inst & Translat Res Inst, Doha, Qatar

来源：

CELLULAR SIGNALLING | 2020年 / 75卷

关键词：

GATA-3; suppression; Adipogenesis; Inflammation; Insulin resistance; Target validation; HUMAN SUBCUTANEOUS ADIPOGENESIS; ADIPOSE-TISSUE; ADIPOCYTE DIFFERENTIATION; TRANSCRIPTION FACTORS; METABOLIC SYNDROME; ACCUMULATION; IMPAIRMENT; ACTIVATION; EXPRESSION; DNAZYME;

D O I：

10.1016/j.cellsig.2020.109735

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Impaired adipogenesis plays an important role in the development of obesity-associated insulin resistance and type 2 diabetes. Adipose tissue inflammation is a crucial mediator of this process. GATA-3 plays important roles in adipogenesis and inflammation. The aim of this study is to investigate the impact of GATA-3 suppression on improving adipogenesis, lowering inflammation and reversing insulin resistance. GATA-3 levels were measured in subcutaneous (SC) and omental (OM) adipose tissues obtained from insulin sensitive (IS) and insulin resistant (IR) obese individuals during weight reduction surgeries. The effect of GATA-3 suppression on adipogenesis, expression of inflammatory cytokines and insulin resistance biomarkers was performed in 3T3L-1 mouse preadipocytes via transfection with GATA-3-specific DNAzyme. GATA-3 expression was higher in OM compared to SC adipose tissues and in stromal vascular fraction-derived differentiating preadipocytes from IR obese individuals compared to their IS counterparts. Suppression of GATA-3 expression in 3T3L-1 mouse preadipocytes with GATA-3 specific inhibitor reversed 4-hydroxynonenal-induced impaired adipogenesis and triggered changes in the expression of insulin signaling-related genes. GATA-3 inhibition also modulated the expression of IL-6 and IL-10 and lowered the expression of insulin resistance biomarkers (PAI-1 and resistin) and insulin resistance phosphoproteins (p-BAD, p-PTEN and p-GSK3 beta). Inhibiting GATA-3 improves adipocytes differentiation, modulates the secretion of inflammatory cytokines and improves insulin sensitivity in insulin resistant cells. Suppression of GATA-3 could be a promising tool to improve adipogenesis, restore insulin sensitivity and lower obesity-associated inflammation in insulin resistant individuals.

引用

页数：7

共 52 条

[41] IL-4-Induced GATA-3 expression is a time-restricted instruction switch for Th2 cell differentiation [J].