Lumican modulates adipocyte function in obesity-associated type 2 diabetes.

IF 3.5 4区 生物学 Q2 ENDOCRINOLOGY & METABOLISM Adipocyte Pub Date : 2022-12-01 DOI:10.1080/21623945.2022.2154112
Clarissa Strieder-Barboza, Carmen G Flesher, Lynn M Geletka, Tad Eichler, Olukemi Akinleye, Alexander Ky, Anne P Ehlers, Carey N Lumeng, Robert W O'Rourke
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Abstract

Obesity-associated type 2 diabetes (DM) leads to adipose tissue dysfunction. Lumican is a proteoglycan implicated in obesity, insulin resistance (IR), and adipocyte dysfunction. Using human visceral adipose tissue (VAT) from subjects with and without DM, we studied lumican effects on adipocyte function. Lumican was increased in VAT and adipocytes in DM. Lumican knockdown in adipocytes decreased lipolysis and improved adipogenesis and insulin sensitivity in VAT adipocytes in DM, while treatment with human recombinant lumican increased lipolysis and impaired insulin-sensitivity in an ERK-dependent manner. We demonstrate that lumican impairs adipocyte metabolism, partially via ERK signalling, and is a potential target for developing adipose tissue-targeted therapeutics in DM.

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Lumican 在肥胖相关的 2 型糖尿病中调节脂肪细胞功能。
与肥胖相关的 2 型糖尿病(DM)会导致脂肪组织功能障碍。Lumican是一种与肥胖、胰岛素抵抗(IR)和脂肪细胞功能障碍有关的蛋白多糖。我们利用患有和未患有糖尿病的受试者的内脏脂肪组织(VAT),研究了Lumican对脂肪细胞功能的影响。在糖尿病患者的内脏脂肪组织和脂肪细胞中,Lumican均有所增加。脂肪细胞中的Lumican敲除减少了脂肪分解,改善了DM患者VAT脂肪细胞的脂肪生成和胰岛素敏感性,而用人类重组lumican处理则增加了脂肪分解,并以ERK依赖的方式损害了胰岛素敏感性。我们证明了lumican会部分通过ERK信号损害脂肪细胞的新陈代谢,是开发针对DM的脂肪组织靶向疗法的潜在靶点。
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来源期刊
Adipocyte
Adipocyte Medicine-Histology
CiteScore
6.50
自引率
3.00%
发文量
46
审稿时长
32 weeks
期刊介绍: Adipocyte recognizes that the adipose tissue is the largest endocrine organ in the body, and explores the link between dysfunctional adipose tissue and the growing number of chronic diseases including diabetes, hypertension, cardiovascular disease and cancer. Historically, the primary function of the adipose tissue was limited to energy storage and thermoregulation. However, a plethora of research over the past 3 decades has recognized the dynamic role of the adipose tissue and its contribution to a variety of physiological processes including reproduction, angiogenesis, apoptosis, inflammation, blood pressure, coagulation, fibrinolysis, immunity and general metabolic homeostasis. The field of Adipose Tissue research has grown tremendously, and Adipocyte is the first international peer-reviewed journal of its kind providing a multi-disciplinary forum for research focusing exclusively on all aspects of adipose tissue physiology and pathophysiology. Adipocyte accepts high-profile submissions in basic, translational and clinical research.
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