Department for the Study of Obesity and Diabetes, Charles University, Prague, Czech Republic.
Franco-Czech Laboratory for Clinical Research on Obesity, Third Faculty of Medicine, Prague and Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, France.
Am J Clin Nutr. 2019 Jun 1;109(6):1499-1510. doi: 10.1093/ajcn/nqy331.
The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders.
Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss.
We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting.
APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor α, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion.
ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.
脂肪组织（AT）是一种分泌器官，可产生多种参与与脂肪量过多相关的代谢紊乱的因子。减肥可改善肥胖相关疾病。
对人体脂肪组织的转录组学研究，以及对从人体脂肪组织分离的脂肪细胞和基质细胞的条件培养基的转录组和蛋白质组分析的综合分析，导致了载脂蛋白 M（apoM）被鉴定为一种潜在的脂肪因子。我们旨在验证 apoM 作为新型脂肪因子，研究 AT APOM 表达与代谢综合征和胰岛素敏感性的关系，并研究其在 AT 中的表达调控及其在热量限制诱导的减肥过程中的分泌。
我们检查了来自 5 项独立临床试验的 485 名个体的 AT 中的 APOM mRNA 水平和分泌，以及人多能脂肪源性干细胞脂肪细胞中的体外表达。在节食期间测量了 APOM 的表达和分泌。
APOM 在人体皮下和内脏脂肪组织中表达，主要由脂肪细胞表达。ApoM 从 AT 释放到循环中，血浆 apoM 浓度与 AT APOM mRNA 水平相关。在 AT 中，APOM 表达与脂肪细胞大小呈负相关，与瘦个体相比，肥胖个体的表达水平较低，并且在代谢综合征和 2 型糖尿病患者中降低。无论脂肪库如何，AT APOM 表达与全身胰岛素敏感性之间均存在正相关关系，与脂肪量和血浆高密度脂蛋白胆固醇无关。在人多能脂肪源性干细胞脂肪细胞中，胰岛素增敏剂过氧化物酶体增殖物激活受体激动剂可增强 APOM 表达，而肿瘤坏死因子α（一种导致胰岛素抵抗的细胞因子）可抑制其表达。在肥胖个体中，热量限制增加了 AT APOM 的表达和分泌。
ApoM 是一种新型的脂肪因子，其表达是健康 AT 的标志，并且可通过热量限制而上调。AT apoM 值得进一步研究，作为糖尿病和心血管疾病风险的潜在生物标志物。
