Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX.
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX.
J Lipid Res. 2011 Jun;52(6):1272-1280. doi: 10.1194/jlr.D012385. Epub 2011 Mar 17.
Recognition of the strength of nonhuman primate models in investigating metabolic disorders has resulted in an expanded need for in vivo research techniques. We studied adipose metabolism in 10 baboons (13.0 ± 4.2 years old, 29.5 ± 5.5 kg). Part 1 evaluated the effect of different sedatives on the rate of appearance of plasma free fatty acids (RaFFA), assessed using ¹³C₄-labeled palmitate infusion (7 µmol/kg/min). Animals, were studied with no sedation, with complete isoflurane sedation, and with minimal midazolam infusion (0.04 mg/kg/h), with the last scheme allowing for the most consistent values and animals that were visually more calm. In Part 2, RaFFA and RaGlycerol (D₅-glycerol, 5 mg/kg lean body mass/h) were measured. From midnight to 0300, flux fell and came to a steady state between 0500 and 0700 h (RaFFA, 39.4 ± 29.8 μmol/kg fat mass/min; and RaGlycerol, 26.9 ± 7.3 μmol/kg/min). The RaFFA-to-RaGlycerol ratio was 1.5 ± 0.8 (49% reesterification). The decline in turnover throughout the night reflects natural circadian processes and was mirrored by reductions in FFA and glycerol to 0.62 and ± 0.14 and 0.16 and ± 0.03 mmol/l, respectively. The concurrent changes in both FFA and glycerol kinetics indicate physiologic validity of the method. These techniques will support needed research to determine mechanisms by which treatments act upon the adipocyte in vivo.
识别非人类灵长类动物模型在研究代谢紊乱方面的优势,导致对体内研究技术的需求扩大。我们研究了 10 只狨猴(13.0 ± 4.2 岁,29.5 ± 5.5 公斤)的脂肪代谢。第 1 部分评估了不同镇静剂对血浆游离脂肪酸(RaFFA)出现率的影响,使用 ¹³C4 标记棕榈酸输注(7 μmol/kg/min)进行评估。在没有镇静剂、完全异氟烷镇静和最小咪达唑仑输注(0.04 mg/kg/h)的情况下研究了动物,最后一种方案允许获得最一致的值和看起来更平静的动物。在第 2 部分,测量了 RaFFA 和 RaGlycerol(D₅-甘油,5 mg/kg 去脂体重/h)。从午夜到 0300,通量下降并在 0500 到 0700 h 之间达到稳定状态(RaFFA,39.4 ± 29.8 μmol/kg 脂肪质量/min;和 RaGlycerol,26.9 ± 7.3 μmol/kg/min)。RaFFA 与 RaGlycerol 的比值为 1.5 ± 0.8(49%再酯化)。整个晚上的周转率下降反映了自然的昼夜节律过程,FFA 和甘油分别下降到 0.62 和 ± 0.14 和 0.16 和 ± 0.03 mmol/l,反映了这一过程。FFA 和甘油动力学的同时变化表明该方法具有生理有效性。这些技术将支持需要的研究,以确定治疗方法在体内作用于脂肪细胞的机制。