Institute of Nutrition and Food Technology, Universidad de Chile, Casilla, Santiago, Chile.
J Endocrinol. 2010 Jul;206(1):75-83. doi: 10.1677/JOE-10-0049. Epub 2010 May 7.
Despite the importance of adipocyte formation for adipose tissue physiology, current knowledge about the mechanisms that regulate the recruitment of progenitor cells to undergo adipogenic differentiation is limited. A role for locally generated angiotensin II emerged from studies with human and murine cells. Preadipose cells from different human fat depots show reduced response to adipogenic stimuli when exposed to angiotensin II. This investigation sought to gain an insight into the intracellular mechanisms involved in the anti-adipogenic response of human preadipose cells from omental fat to angiotensin II. Its effect was evaluated on cells stimulated to adipogenic differentiation in vitro, by assessment of glycerol-3-phosphate dehydrogenase activity and expression of early markers of adipogenesis. Extracellular signal-regulated kinase(1,2) (ERK(1,2)) pathway activation was inferred from the phosphorylated to total ERK(1,2) ratio determined by western blot. Exposure to angiotensin II throughout the 10-day differentiation period resulted in a reduced adipogenic response. A similar anti-adipogenic effect was observed when this hormone was present during the first 48 h of induction to differentiation. Angiotensin II treatment had no consequences on CCAAT/enhancer-binding protein beta and peroxisome proliferator-activated receptor gamma (PPARG) induction, but increased the phosphorylated form of the key adipogenic regulator PPARG. Upon angiotensin II exposure, a raise of phosphorylated ERK(1,2) was determined, which was more prominent 8-20 h after induction of adipogenesis (when controls reached negligible values). Chemical inhibition of ERK(1,2) phosphorylation prevented angiotensin II-dependent reduction in adipogenesis. These results support the participation of the mitogen-activated protein kinase/ERK(1,2) pathway in the anti-adipogenic effect of angiotensin II on preadipose cells from human omental adipose tissue.
尽管脂肪细胞形成对于脂肪组织生理学非常重要，但目前对于调节祖细胞募集以进行脂肪生成分化的机制知之甚少。局部产生的血管紧张素 II 的作用是从人类和鼠细胞的研究中得出的。来自不同人体脂肪沉积物的前脂肪细胞在暴露于血管紧张素 II 时对脂肪生成刺激的反应降低。本研究旨在深入了解人网膜脂肪前脂肪细胞对血管紧张素 II 的抗脂肪生成反应所涉及的细胞内机制。通过评估甘油-3-磷酸脱氢酶活性和脂肪生成早期标志物的表达，评估其对体外刺激脂肪生成分化的细胞的影响。通过 Western blot 测定磷酸化 ERK(1,2)与总 ERK(1,2)的比值来推断细胞外信号调节激酶(1,2) (ERK(1,2))途径的激活。在整个 10 天分化期间暴露于血管紧张素 II 导致脂肪生成反应降低。当这种激素存在于诱导分化的前 48 小时时，观察到类似的抗脂肪生成作用。血管紧张素 II 处理对 CCAAT/增强子结合蛋白β和过氧化物酶体增殖物激活受体γ (PPARG)的诱导没有影响，但增加了关键脂肪生成调节剂 PPARG 的磷酸化形式。暴露于血管紧张素 II 后，确定了磷酸化 ERK(1,2)的升高，在诱导脂肪生成 8-20 小时后更为明显（此时对照达到可忽略的值）。ERK(1,2)磷酸化的化学抑制阻止了血管紧张素 II 依赖性脂肪生成减少。这些结果支持丝裂原激活蛋白激酶/ERK(1,2)途径参与血管紧张素 II 对人网膜脂肪前脂肪细胞的抗脂肪生成作用。
