AIMS Obesity is associated with adipose tissue (AT) dysfunction marked by cellular hypertrophy, inflammation, hypoxia and fibrosis. Angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase which regulates triglyceride storage. Recently, inhibition of ANGPTL4 has been suggested as potential treatment for type 2 diabetes. Here we evaluate ANGPTL4's role in diabetes and examine ANGPTL4 in relation to markers of AT dysfunction and fatty liver disease. MATERIALS & METHODS We obtained a unique set of paired samples from subjects undergoing weight loss surgery including subcutaneous AT (SCAT), omental AT (OMAT), liver, thigh muscle biopsies and serum including a post-surgical SCAT biopsy after 9 months. RESULTS SCAT ANGPTL4 expression and circulating protein levels were higher in people with diabetes and correlated with glucose levels and HOMA-IR but not BMI. At post-surgical follow up, SCAT ANGPTL4 declined in subjects with diabetes to levels of those without diabetes. ANGPTL4 expression correlated with HIF1A and inflammation (MCP-1, IL-6). CONCLUSIONS We found that SCAT ANGPTL4 was closely linked with the expression of ANGPTL4 in the liver and represented a good proxy for liver steatosis. We suggest the elevation of ANGPTL4 levels in diabetes and the association with inflammation and hypoxia is due to a compensatory mechanism to limit further AT dysfunction. A reduction of ANGPTL4 for the treatment of T2DM as previously suggested is thus unlikely to be of further benefit.

中文翻译：

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人2型糖尿病中血管生成素样蛋白4的循环和组织特异性转录。

AIMS肥胖与以细胞肥大，炎症，缺氧和纤维化为特征的脂肪组织（AT）功能障碍有关。血管生成素样蛋白4（ANGPTL4）抑制脂蛋白脂肪酶，后者调节甘油三酸酯的储存。近来，已提出抑制ANGPTL4作为2型糖尿病的潜在治疗方法。在这里，我们评估ANGPTL4在糖尿病中的作用，并检查ANGPTL4与AT功能障碍和脂肪肝疾病标志物的关系。材料与方法我们从接受减肥手术的受试者（包括皮下AT（SCAT），网膜AT（OMAT），肝脏，大腿肌肉活检和血清，包括术后9个月的SCAT活检）中获得了一组独特的配对样本。结果在糖尿病患者中，SCAT ANGPTL4表达和循环蛋白水平较高，并且与葡萄糖水平和HOMA-IR相关，而与BMI相关。在手术后的随访中，患有糖尿病的受试者的SCAT ANGPTL4降至未患有糖尿病的受试者的水平。ANGPTL4表达与HIF1A和炎症（MCP-1，IL-6）相关。结论我们发现SCAT ANGPTL4与ANGPTL4在肝脏中的表达密切相关，并代表了肝脂肪变性的良好代理。我们认为糖尿病中ANGPTL4水平的升高以及与炎症和缺氧的关系是由于补偿机制限制了进一步的AT功能障碍。因此，如先前所建议的减少ANGPTL4用于治疗T2DM不太可能进一步受益。SCAT ANGPTL4在患有糖尿病的受试者中降至未患有糖尿病的受试者的水平。ANGPTL4表达与HIF1A和炎症（MCP-1，IL-6）相关。结论我们发现SCAT ANGPTL4与ANGPTL4在肝脏中的表达密切相关，并代表了肝脂肪变性的良好代理。我们认为糖尿病中ANGPTL4水平的升高以及与炎症和缺氧的关系是由于补偿机制限制了进一步的AT功能障碍。因此，如先前所建议的减少ANGPTL4用于治疗T2DM不太可能进一步受益。SCAT ANGPTL4在患有糖尿病的受试者中降至未患有糖尿病的受试者的水平。ANGPTL4表达与HIF1A和炎症（MCP-1，IL-6）相关。结论我们发现SCAT ANGPTL4与ANGPTL4在肝脏中的表达密切相关，并代表了肝脂肪变性的良好代理。我们认为糖尿病中ANGPTL4水平的升高以及与炎症和缺氧的关系是由于补偿机制限制了进一步的AT功能障碍。因此，如先前所建议的减少ANGPTL4用于治疗T2DM不太可能进一步受益。结论我们发现SCAT ANGPTL4与ANGPTL4在肝脏中的表达密切相关，并代表了肝脂肪变性的良好代理。我们认为糖尿病中ANGPTL4水平的升高以及与炎症和缺氧的关系是由于补偿机制限制了进一步的AT功能障碍。因此，如先前所建议的减少ANGPTL4用于治疗T2DM不太可能进一步受益。结论我们发现SCAT ANGPTL4与ANGPTL4在肝脏中的表达密切相关，并代表了肝脂肪变性的良好代理。我们认为糖尿病中ANGPTL4水平的升高以及与炎症和缺氧的关系是由于补偿机制限制了进一步的AT功能障碍。因此，如先前所建议的减少ANGPTL4用于治疗T2DM不太可能进一步受益。