ERI22-EA4173, faculté Rockefeller, UCB Lyon 1, 8, avenue Rockfeller, 69008 Lyon, France.
Diabetes Metab. 2010 Jun;36(3):221-8. doi: 10.1016/j.diabet.2010.01.003. Epub 2010 Mar 19.
Lipogenesis is expressed in vascular smooth muscle cells (VSMCs), and such in situ lipogenesis could be providing the fatty acids for triglyceride synthesis and cholesterol esterification, and contributing to lipid accumulation in the arterial wall. This study investigated both the expression and regulation of lipogenesis in VSMCs to determine if they are modified in Psammomys obesus gerbils fed a high-fat diet as a model of insulin resistance and diabetes.
Aortas were collected from diabetic and non-diabetic P. obesus for histological examination, measurement of lipogenic gene expression and VSMC culture.
The aortas of diabetic animals exhibited lipid deposits and foam cells as well as disorganization of elastic fibres. However, lipogenic gene expression was not modified. VSMCs in vitro from the aortas of diabetic animals had, compared with cells from non-diabetic animals, lower mRNA levels of SREBP-1c and ChREBP. An adipogenic medium stimulated moderate FAS and ACC1 expression in cells from both diabetic and non-diabetic animals, but glucose and insulin on their own had no such stimulatory action. Also, triiodothyronine (T3) had a clear stimulatory action, while angiotensin II had a moderate effect, in cells from non-diabetic P. obesus, but not from diabetic animals, whereas LXR agonists stimulated lipogenesis in cells from both animal groups.
Lipogenesis is expressed in the arterial walls and VSMCs of P. obesus. However, its expression was not increased in diabetes, and did not respond to either T3 or angiotensin II. Therefore, lipogenesis in situ is unlikely to contribute to the accumulation of lipids in the arterial walls of diabetic P. obesus gerbils.
血管平滑肌细胞(VSMCs)中存在脂生成,这种原位脂生成可能为甘油三酯合成和胆固醇酯化提供脂肪酸,并导致动脉壁中的脂质积累。本研究调查了 VSMCs 中脂生成的表达和调节,以确定胰岛素抵抗和糖尿病模型中高脂饮食喂养的沙鼠是否改变了其脂生成。
收集糖尿病和非糖尿病 P. obesus 的主动脉进行组织学检查、脂生成基因表达和 VSMC 培养测量。
糖尿病动物的主动脉表现出脂质沉积和泡沫细胞,以及弹性纤维的紊乱。然而,脂生成基因表达没有改变。与非糖尿病动物的细胞相比,糖尿病动物主动脉来源的 VSMCs 中 SREBP-1c 和 ChREBP 的 mRNA 水平较低。与细胞相比,脂肪生成培养基刺激来自糖尿病和非糖尿病动物的细胞中等 FAS 和 ACC1 表达,但葡萄糖和胰岛素本身没有这种刺激作用。此外,三碘甲状腺原氨酸(T3)对非糖尿病 P. obesus 的细胞有明显的刺激作用,而血管紧张素 II 有适度的作用,但对糖尿病动物的细胞没有作用,而 LXR 激动剂刺激两组动物的细胞中的脂生成。
脂生成在 P. obesus 的动脉壁和 VSMCs 中表达。然而,在糖尿病中其表达没有增加,并且对 T3 或血管紧张素 II 没有反应。因此,原位脂生成不太可能导致糖尿病 P. obesus 沙鼠动脉壁中脂质的积累。