Rittig Nikolaj, Svart Mads, Jessen Niels, Møller Niels, Møller Holger J, Grønbæk Henning
Department of Internal Medicine and Endocrinology (MEA) and Medical Research LaboratoryAarhus University Hospital, Aarhus C, Denmark
Department of Internal Medicine and Endocrinology (MEA) and Medical Research LaboratoryAarhus University Hospital, Aarhus C, Denmark.
Endocr Connect. 2018 Jan;7(1):107-114. doi: 10.1530/EC-17-0296.
Macrophage activation determined by levels of soluble sCD163 is associated with obesity, insulin resistance, diabetes mellitus type 2 (DM2) and non-alcoholic fatty liver disease (NAFLD). This suggests that macrophage activation is involved in the pathogenesis of conditions is characterised by adaptions in the lipid metabolism. Since sCD163 is shed to serum by inflammatory signals including lipopolysaccharides (LPS, endotoxin), we investigated sCD163 and correlations with lipid metabolism following LPS exposure.
Eight healthy male subjects were investigated on two separate occasions: (i) following an LPS exposure and (ii) following saline exposure. Each study day consisted of a four-hour non-insulin-stimulated period followed by a two-hour hyperinsulinemic euglycemic clamp period. A H-palmitate tracer was used to calculate the rate of appearance (Ra). Blood samples were consecutively obtained throughout each study day. Abdominal subcutaneous adipose tissue was obtained for western blotting.
We observed a significant two-fold increase in plasma sCD163 levels following LPS exposure ( < 0.001), and sCD163 concentrations correlated positively with the plasma concentration of free fatty acids, Ra, lipid oxidation rates and phosphorylation of the hormone-sensitive lipase at serine 660 in adipose tissue ( < 0.05, all). Furthermore, sCD163 concentrations correlated positively with plasma concentrations of cortisol, glucagon, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 ( < 0.05, all).
We observed a strong correlation between sCD163 and stimulation of lipolysis and fat oxidation following LPS exposure. These findings support preexisting theory that inflammation and macrophage activation play a significant role in lipid metabolic adaptions under conditions such as obesity, DM2 and NAFLD.
由可溶性sCD163水平所决定的巨噬细胞活化与肥胖、胰岛素抵抗、2型糖尿病（DM2）及非酒精性脂肪性肝病（NAFLD）相关。这表明巨噬细胞活化参与了以脂质代谢适应性变化为特征的疾病的发病机制。由于sCD163可通过包括脂多糖（LPS，内毒素）在内的炎症信号释放至血清中，我们研究了LPS暴露后sCD163及其与脂质代谢的相关性。
对8名健康男性受试者进行了两次单独的研究：（i）LPS暴露后；（ii）生理盐水暴露后。每个研究日包括4小时的非胰岛素刺激期，随后是2小时的高胰岛素正常血糖钳夹期。使用H-棕榈酸示踪剂计算出现率（Ra）。在每个研究日连续采集血样。获取腹部皮下脂肪组织用于蛋白质印迹分析。
我们观察到LPS暴露后血浆sCD163水平显著升高两倍（<0.001），且sCD163浓度与游离脂肪酸的血浆浓度、Ra、脂质氧化率以及脂肪组织中丝氨酸660位点的激素敏感性脂肪酶磷酸化呈正相关（均<0.
