C1q/TNF-Related Protein 3 (CTRP-3) Deficiency of Adipocytes Affects White Adipose Tissue Mass but Not Systemic CTRP-3 Concentrations.

C1q/TNF-Related Protein 3 (CTRP-3) Deficiency of Adipocytes Affects White Adipose Tissue Mass but Not Systemic CTRP-3 Concentrations.
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DOI:
10.3390/ijms22041670
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发表时间:
2021-02-07
影响因子:
5.6
通讯作者:
Schäffler A
Schäffler A
中科院分区:
生物学2区
文献类型:
--
作者:
Schmid A;Roderfeld M;Gehl J;Roeb E;Nist A;Chung HR;Stiewe T;Karrasch T;Schäffler A

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CTRP-3(C1 q/TNF-related protein-3)是一种具有内分泌和免疫功能的脂肪因子。脂肪细胞CTRP-3产生对全身CTRP-3浓度和脂肪细胞生物学的影响尚不清楚。建立脂肪细胞CTRP-3敲除(KO)的鼠模型(通过Cre/loxP系统)。通过ELISA定量血清脂肪因子水平,通过实时PCR定量脂肪组织(AT)基因表达。从AT中分离前脂肪细胞并分化为脂肪细胞。比较转录组分析应用于脂肪细胞和肝组织。CTRP-3 KO小鼠的体重和AT质量降低,血清瘦素降低。在KO小鼠内脏AT的原代细胞中,脂联素、颗粒蛋白前体和β-淀粉样蛋白的表达被诱导,而过氧化物酶体增殖物激活受体γ(过氧化物酶体增殖物激活受体γ)的表达被降低。M1/M2巨噬细胞极化标志物转变为更具抗炎性的表型。AT中CTRP-3的表达对血清浓度没有贡献。AT和肝脏形态不受CTRP-3 KO的影响。髓磷脂转录因子1样(Myt 11)被确定为一个高度上调的基因。总之,脂肪细胞CTRP-3在脂肪形成和AT体重增加中起作用,而脂肪细胞分化不受CTRP-3缺乏的影响。由于未观察到对循环CTRP-3水平的影响,因此脂肪细胞CTRP-3 KO的影响仅限于脂肪组织。修饰的AT基因表达指示相当抗炎的表型。
CTRP-3 (C1q/TNF-related protein-3) is an adipokine with endocrine and immunological function. The impact of adipocyte CTRP-3 production on systemic CTRP-3 concentrations and on adipocyte biology is unknown. A murine model of adipocyte CTRP-3 knockout (KO) was established (via the Cre/loxP system). Serum adipokine levels were quantified by ELISA and adipose tissue (AT) gene expression by real-time PCR. Preadipocytes were isolated from AT and differentiated into adipocytes. Comparative transcriptome analysis was applied in adipocytes and liver tissue. Body weight and AT mass were reduced in CTRP-3 KO mice together with decreased serum leptin. In primary cells from visceral AT of KO mice, expression of adiponectin, progranulin, and resistin was induced, while peroxisome proliferator activated receptor γ (PPARγ) was decreased. M1/M2 macrophage polarization markers were shifted to a more anti-inflammatory phenotype. CTRP-3 expression in AT did not contribute to serum concentrations. AT and liver morphology remained unaffected by CTRP-3 KO. Myelin transcription factor 1-like (Myt1l) was identified as a highly upregulated gene. In conclusion, adipocyte CTRP-3 has a role in adipogenesis and AT weight gain whereas adipocyte differentiation is not impaired by CTRP-3 deficiency. Since no effects on circulating CTRP-3 levels were observed, the impact of adipocyte CTRP-3 KO is limited to adipose tissue. Modified AT gene expression indicates a rather anti-inflammatory phenotype.
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