1Section of Diabetes, Endocrinology and Nutrition, Hospital of Girona "Dr Josep Trueta," Carretera de França s/n, 17007, Girona, Spain.
FASEB J. 2014 Mar;28(3):1071-81. doi: 10.1096/fj.13-234419. Epub 2013 Nov 21.
Despite their differential effects on human metabolic pathophysiology, the differences in omental and subcutaneous lipidomes are largely unknown. To explore this field, liquid chromatography coupled with mass spectrometry was used for lipidome analyses of adipose tissue samples (visceral and subcutaneous) selected from a group of obese subjects (n=38). Transcriptomics and in vitro studies in adipocytes were used to confirm the pathways affected by location. The analyses revealed the existence of obesity-related specific lipidome signatures in each of these locations, attributed to selective enrichment of specific triglycerides, glycerophospholipids, and sphingolipids, because these were not observed in adipose tissues from nonobese individuals. The changes were compatible with subcutaneous enrichment in pathways involved in adipogenesis, triacylglyceride synthesis, and lipid droplet formation, as well as increased α-oxidation. Marked differences between omental and subcutaneous depots in obese individuals were seen in the association of lipid species with metabolic traits (body mass index and insulin sensitivity). Targeted studies also revealed increased cholesterol (Δ56%) and cholesterol epoxide (Δ34%) concentrations in omental adipose tissue. In view of the effects of cholesterol epoxide, which induced enhanced expression of adipocyte differentiation and α-oxidation genes in human omental adipocytes, a novel role for cholesterol epoxide as a signaling molecule for differentiation is proposed. In summary, in obesity, adipose tissue exhibits a location-specific differential lipid profile that may contribute to explaining part of its distinct pathogenic role.
尽管它们对人类代谢病理生理学的影响存在差异,但网膜和皮下脂质组之间的差异在很大程度上尚不清楚。为了探索这一领域,我们使用液相色谱-质谱联用技术对一组肥胖受试者(n=38)的脂肪组织样本(内脏和皮下)进行了脂质组分析。通过对脂肪细胞进行转录组学和体外研究,证实了位置影响的途径。分析结果显示,在这些部位存在与肥胖相关的特定脂质组特征,这归因于特定甘油三酯、甘油磷脂和神经酰胺的选择性富集,而在非肥胖个体的脂肪组织中则未观察到这些脂质。这些变化与皮下脂肪组织中涉及脂肪生成、甘油三酯合成和脂滴形成的途径的富集以及α-氧化增加是一致的。在肥胖个体中,网膜和皮下脂肪组织之间存在明显的差异,脂质种类与代谢特征(体重指数和胰岛素敏感性)之间存在关联。靶向研究还揭示了网膜脂肪组织中胆固醇(增加 56%)和胆固醇环氧化物(增加 34%)浓度的增加。鉴于胆固醇环氧化物可诱导人网膜脂肪细胞中脂肪细胞分化和α-氧化基因的表达增强,提出胆固醇环氧化物作为分化信号分子的新作用。总之,在肥胖中,脂肪组织表现出特定部位的差异脂质谱,这可能有助于解释其独特的发病作用的一部分。