Lacroix Delphine, Moutel Sandrine, Coupaye Muriel, Huvenne Hélène, Faucher Pauline, Pelloux Véronique, Rouault Christine, Bastard Jean-Philippe, Cagnard Nicolas, Dubern Béatrice, Clément Karine, Poitou Christine
INSERM, U1166, Nutriomic team 6 (D.L., H.H., V.P., C.R., B.D., K.C., C.P.), Sorbonne Universities (D.L., H.H., V.P., C.R., B.D., K.C., C.P.), University Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche en Santé Unité 1166, and Institute of Cardiometabolism and Nutrition (ICAN) (S.M., M.C., P.F., K.C., C.P.), Assistance Publique Hôpitaux de Paris, Department of Nutrition, and French Reference Centre for Prader-Willi Syndrome, Pitié-Salpêtrière Hospital, Paris, F-75013 France; Functional Unit of Inflammatory and Metabolic Biomarkers (J.-P.B.), Department of Biochemistry and Hormonology, Tenon Hospital, Assistance Publique des Hôpitaux de Paris, F-75970 Paris, France; Bioinformatics Platform (N.C.), Plateforme de Bioinformatique, SFR Necker, University Paris V, F-75015 Paris, France; and Department of Pediatric Nutrition and Gastroenterology (B.D.), Trousseau Hospital, Assistance Publique Hôpitaux de Paris, F-37044 Paris, France.
J Clin Endocrinol Metab. 2015 Mar;100(3):850-9. doi: 10.1210/jc.2014-3127. Epub 2014 Dec 5.
Prader-Willi syndrome (PWS), the most frequent syndrome of obesity, is a model of early fat mass (FM) development, but scarce data exist on adipose tissue characteristics.
The objective of the study was to compare metabolic, fat distribution, and transcriptomic signatures of sc adipose tissue (scAT) in PWS adults, with matched obese adults with primary obesities.
Hormonal and metabolic assessments, systemic inflammation, and gene expression in scAT were compared between PWS patients and obese controls (OCs). Each 42nd PWS patient was matched with one randomly paired control with primary obesity. Matching factors were age, gender, fat mass (percentage), and diabetic status.
Compared with OCs, the PWS group had a decreased percentage of trunk FM and a better metabolic profile with decreased insulin and homeostasis model assessment, an index of insulin-resistance, and increased concentrations of serum adiponectin and ghrelin. Adipocyte size relative to body fat was significantly higher in PWS vs OCs. scAT in PWS patients was characterized by a transcriptomic functional signature with enrichment of themes related to immunoinflammation, the extracellular matrix, and angiogenesis. A RT-PCR targeted study revealed that candidate genes encoding proinflammatory markers and remodeling molecules, CD68, CD3e, IL-1β, chemokine (C-C motif) ligand 5, collagen type 4-α, and lysyl oxidase, were down-regulated.
Matched for FM, PWS subjects have a better metabolic profile, a phenotype that could be linked to changes in scAT remodeling and promotion of adipocyte growth.
普拉德-威利综合征（PWS）是最常见的肥胖综合征，是早期脂肪量（FM）发育的模型，但关于脂肪组织特征的数据稀少。
本研究的目的是比较PWS成年患者与匹配的原发性肥胖成年肥胖患者皮下脂肪组织（scAT）的代谢、脂肪分布和转录组特征。
比较了PWS患者和肥胖对照组（OCs）之间的激素和代谢评估、全身炎症以及scAT中的基因表达。每42名PWS患者与一名随机配对的原发性肥胖对照进行匹配。匹配因素包括年龄、性别、脂肪量（百分比）和糖尿病状态。
与OCs相比，PWS组躯干FM百分比降低，代谢状况更好，胰岛素和胰岛素抵抗指数稳态模型评估降低，血清脂联素和胃饥饿素浓度升高。PWS患者相对于体脂的脂肪细胞大小明显高于OCs。PWS患者的scAT具有转录组功能特征，与免疫炎症、细胞外基质和血管生成相关的主题富集。一项靶向RT-PCR研究显示，编码促炎标志物和重塑分子的候选基因，如CD68、CD3e、IL-1β、趋化因子（C-C基序）配体5、4型胶原-α和赖氨酰氧化酶，表达下调。
在FM匹配的情况下，PWS受试者具有更好的代谢状况，这种表型可能与scAT重塑的变化和脂肪细胞生长的促进有关。
