Roth Jonathan D, Hughes Heather, Coffey Todd, Maier Holly, Trevaskis James L, Anderson Christen M
Amylin Pharmaceuticals, Inc., 9360 Towne Centre Dr., San Diego, CA 92121, USA.
Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E1112-7. doi: 10.1152/ajpendo.00395.2007. Epub 2007 Aug 14.
Amylin infusion reduces food intake and slows body weight gain in rodents. In obese male rats, amylin (but not pair feeding) caused a preferential reduction of fat mass with protein preservation despite equal body weight loss in amylin-treated (fed ad libitum) and pair-fed rats. In the present study, the effect of prior or concurrent food restriction on the ability of amylin to cause weight loss was evaluated. Retired female breeder rats were maintained on a high-fat diet (40% fat) for 9 wk. Prior to drug treatment, rats were either fed ad libitum or food restricted for 10 days to lose 5% of their starting body weight. They were then subdivided into treatment groups that received either vehicle or amylin (100 microgxkg(-1)xday(-1) via subcutaneous minipump) and placed under either a restricted or ad libitum feeding schedule (for a total of 8 treatment arms). Amylin 1) significantly reduced body weight compared with vehicle under all treatment conditions, except in always restricted animals, 2) significantly decreased percent body fat in all groups, and 3) preserved lean mass in all groups. These results indicate that amylin's anorexigenic and fat-specific weight loss properties can be extended to a variety of nutritive states in female rats.
注射胰岛淀粉样多肽可减少啮齿动物的食物摄入量并减缓体重增加。在肥胖雄性大鼠中，胰岛淀粉样多肽（而非配对喂养）可在胰岛淀粉样多肽处理组（自由进食）和配对喂养组体重同等下降的情况下，优先减少脂肪量并保留蛋白质。在本研究中，评估了预先或同时进行食物限制对胰岛淀粉样多肽导致体重减轻能力的影响。将退役的雌性繁殖大鼠维持在高脂肪饮食（40%脂肪）9周。在药物治疗前，大鼠要么自由进食，要么食物限制10天以减轻起始体重的5%。然后将它们细分为接受载体或胰岛淀粉样多肽（通过皮下微型泵，100μg·kg⁻¹·天⁻¹）的治疗组，并置于限制或自由进食方案下（总共8个治疗组）。胰岛淀粉样多肽1）在所有治疗条件下与载体相比均显著降低体重，但始终处于限制饮食的动物除外；2）在所有组中均显著降低体脂百分比；3）在所有组中均保留瘦体重。这些结果表明，胰岛淀粉样多肽的厌食和特定于脂肪组织的减肥特性可扩展至雌性大鼠的多种营养状态。
