Polus Anna, Kiec-Wilk Beata, Razny Urszula, Gielicz Anna, Schmitz Gerd, Dembinska-Kiec Aldona
Department of Clinical Biochemistry Collegium Medicum, Jagiellonian University, Cracow, Poland.
Department of Metabolic Diseases Collegium Medicum, Jagiellonian University, Cracow, Poland.
Biochim Biophys Acta. 2015 Sep;1851(9):1146-55. doi: 10.1016/j.bbalip.2015.05.002. Epub 2015 May 9.
Mediators such as cytokines, eicosanoids, nitric oxide and growth factors may regulate adipogenesis as well as inflammation. It is well documented that production of some form of eicosanoids activates lipid synthesis during adipogenesis but also contributes to the formation of factors maintaining low-level systemic inflammation. Developing nutrients for reduction of adipogenesis and inflammation can enhance preventive efficacy of daily diet. This study examined the effects of free fatty acid influence on changes in lipid biosynthesis and corresponding gene expression during differentiation of human subcutaneous adipose tissue stromal vascular fraction (SVF) cells. Proadipogenic conditions promoted SVF cell differentiation and lipid droplet (LD) formation up to 15 days. This correlated with gene expression of adipocyte differentiation markers as well as inflammatory cytokines and their receptors. Addition of free fatty acids to differentiation medium increased their incorporation during the first period of differentiation (48 h). Presence of eicosanoid acid (EPA) during the initial period of differentiation by elevation of Perilipin 3 protein (TIP47), may be responsible for smaller LD formation. Presence of arachidonic acid (AA) tends to deposit lipids in large form of LDs. Prolongation of differentiation up to 15 days decreased AA or EPA in cellular lipids. PUFA through up-regulation of both phospholipase 2 and enzymes related to eicosanoid production influenced type and quantity of eicosanoids which regulated the extent of SVF cell differentiation. Formation of small LDs and reduction of pro-inflammatory mediators in adipose tissue are the consequence of eicosanoid production with anti-inflammatory potential from EPA.
细胞因子、类二十烷酸、一氧化氮和生长因子等介质可能会调节脂肪生成以及炎症反应。有充分的文献记载,某种形式的类二十烷酸的产生在脂肪生成过程中会激活脂质合成,但也有助于形成维持低水平全身炎症的因子。开发用于减少脂肪生成和炎症的营养物质可以提高日常饮食的预防功效。本研究考察了游离脂肪酸对人皮下脂肪组织基质血管成分(SVF)细胞分化过程中脂质生物合成变化及相应基因表达的影响。促脂肪生成条件促进SVF细胞分化和脂滴(LD)形成,持续长达15天。这与脂肪细胞分化标志物以及炎性细胞因子及其受体的基因表达相关。在分化培养基中添加游离脂肪酸会增加其在分化初期(48小时)的掺入。在分化初期存在二十碳五烯酸(EPA)通过升高 perilipin 3蛋白(TIP47),可能是导致较小脂滴形成的原因。花生四烯酸(AA)的存在倾向于以大脂滴形式沉积脂质。将分化延长至15天会降低细胞脂质中的AA或EPA。多不饱和脂肪酸通过上调磷脂酶2和与类二十烷酸产生相关的酶,影响了调节SVF细胞分化程度的类二十烷酸的类型和数量。脂肪组织中小脂滴的形成和促炎介质的减少是由具有抗炎潜力的EPA产生类二十烷酸的结果。