Department of Immunology and Molecular Pathology, University College London Medical School, UK.
Biogerontology. 2010 Aug;11(4):483-93. doi: 10.1007/s10522-010-9271-x. Epub 2010 Mar 25.
Adipose tissue plays a pivotal role in ageing and longevity; many studies, both human and animal, have focussed on the effects of food limitation. Here we present a new model based on striking differences between two 'normal' inbred strains of albino Wistar rats the Charles River (CR) and Harlan Olac (HO) that have marked differences in age-related accumulation of fat and insulin-stimulated rates of glucose incorporation into lipid in the epididymal fat pads (EFP). The incorporation [U-(14)C]glucose into lipid by adipocytes showed that the CR group had a twofold higher basal rate of lipogenesis and a greater response to insulin in vitro, exceptionally, adipocytes from CR group maintained the high response to insulin to late adulthood while retaining the lower EFP weight/100 g body weight. Inositol phosphoglycan A-type (IPG-A), a putative insulin second messenger, was 3.5-fold higher and cAMP significantly lower per EFP in the CR versus HO groups. Plasma insulin levels were similar and plasma leptin higher in CR versus HO groups. The anomaly of a higher rate of lipogenesis and response to insulin and lower EFP weight in the CR group is interpreted as the resultant effect of a faster turnover of lipid and stimulating effect of leptin in raising fatty acid oxidation by muscle, potentially key to the lower accumulation of visceral fat. The metabolic profile of the CR strain provides a template that could be central to therapies that may lead to the lowering of both adipose and non-adipocyte lipid accumulation in humans in ageing.
脂肪组织在衰老和长寿中起着关键作用；许多人类和动物的研究都集中在食物限制的影响上。在这里，我们提出了一个新的模型，该模型基于白化 Wistar 大鼠两个“正常”近交系——Charles River（CR）和 Harlan Olac（HO）之间的显著差异，这两个系在与年龄相关的脂肪积累和胰岛素刺激的附睾脂肪垫（EFP）中葡萄糖掺入脂质的速率方面存在明显差异。脂肪细胞对[U-（14）C]葡萄糖的掺入表明，CR 组的基础脂肪生成率高出两倍，体外对胰岛素的反应更大，异常的是，CR 组的脂肪细胞在保留较低的 EFP 重量/100g 体重的同时，仍保持对胰岛素的高反应性至老年。肌醇磷酸聚糖 A 型（IPG-A），一种假定的胰岛素第二信使，在 CR 与 HO 组中每 EFP 的含量高出 3.5 倍，cAMP 显著降低。CR 组与 HO 组的血浆胰岛素水平相似，而血浆瘦素水平更高。CR 组的脂肪生成率和胰岛素反应更高，EFP 重量更低的异常情况被解释为脂质周转率更快和瘦素刺激作用的结果，这可能是肌肉中脂肪酸氧化升高的关键，潜在地降低内脏脂肪的积累。CR 品系的代谢特征提供了一个模板，可能是降低衰老过程中人类脂肪和非脂肪细胞脂质积累的关键。
