Department of Medicine (H7), Karolinska Institutet, 141 86, Stockholm, Sweden.
Inserm, UMR 1048, Team 1, I2MC, Institute of Metabolic and Cardiovascular Diseases, BP84225, 31432, Toulouse Cedex 4, France.
Int J Obes (Lond). 2018 Dec;42(12):2047-2056. doi: 10.1038/s41366-018-0018-0. Epub 2018 Jan 30.
Adipokines are peptides secreted from white adipose tissue (WAT), which have been linked to WAT dysfunction and metabolic complications of obesity. We set out to identify novel adipokines in subcutaneous WAT (sWAT) linked to insulin resistance (IR).
Gene expression was determined by microarray and qPCR in obese and non-obese subjects with varying degree of IR. WAT-secreted and circulating protein levels were measured by ELISA.
In sWAT of 80 obese women discordant for IR, 44 genes encoding potential adipose-secreted proteins were differentially expressed. Among these, merely two proteins, S100A4 and MXRA5 were released from sWAT in a time-dependent manner (criterion for true adipokines) but only the circulating levels of S100A4 were higher in IR. In two additional cohorts (n = 29 and n = 56), sWAT S100A4 secretion was positively and BMI-independently associated with IR (determined by clamp or HOMA-IR), ATP-III risk score and adipocyte size (hypertrophy). In non-obese (n = 20) and obese subjects before and after bariatric surgery (n = 21), circulating and sWAT-secreted levels were highest in the obese and normalized following weight loss. Serum S100A4 concentrations were higher in subjects with type 2 diabetes. S100A4 sWAT expression associated positively with genes involved in inflammation/extracellular matrix formation and inversely with genes in metabolic pathways. Although S100A4 was expressed in both stromal cells and adipocytes, only the expression in adipocytes associated with BMI.
S100A4 is a novel adipokine associated with IR and sWAT inflammation/adipocyte hypertrophy independently of BMI. Its value as a circulating marker for dysfunctional WAT and IR needs to be validated in larger cohorts.
脂肪细胞因子是由白色脂肪组织（WAT）分泌的肽类物质，与 WAT 功能障碍和肥胖的代谢并发症有关。我们旨在确定与胰岛素抵抗（IR）相关的新的脂肪细胞因子。
通过微阵列和 qPCR 确定肥胖且存在不同程度 IR 的患者的脂肪组织中基因的表达情况。通过 ELISA 测定脂肪组织分泌和循环的蛋白质水平。
在 80 名肥胖且存在 IR 差异的女性的皮下 WAT 中，44 个编码潜在脂肪分泌蛋白的基因表达不同。其中，只有两种蛋白质，S100A4 和 MXRA5，以时间依赖性方式从 sWAT 中释放（作为真正的脂肪细胞因子的标准），但仅 S100A4 的循环水平在 IR 中更高。在另外两个队列（n=29 和 n=56）中，sWAT S100A4 的分泌与 IR（通过钳夹或 HOMA-IR 确定）、ATP-III 风险评分和脂肪细胞大小（肥大）呈正相关，且与 BMI 无关。在非肥胖（n=20）和肥胖患者在减重手术前后（n=21），肥胖患者的循环和 sWAT 分泌水平最高，减肥后恢复正常。2 型糖尿病患者的血清 S100A4 浓度较高。S100A4 sWAT 的表达与炎症/细胞外基质形成相关基因呈正相关，与代谢途径相关基因呈负相关。尽管 S100A4 在基质细胞和脂肪细胞中均有表达，但只有脂肪细胞中的表达与 BMI 相关。
S100A4 是一种与 IR 和 sWAT 炎症/脂肪细胞肥大相关的新型脂肪细胞因子，与 BMI 无关。需要在更大的队列中验证其作为功能失调的 WAT 和 IR 的循环标志物的价值。
