Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, Regenerative Medicine Research Center, Sichuan, PR China.
Exp Biol Med (Maywood). 2012 Nov;237(11):1310-21. doi: 10.1258/ebm.2012.012157.
Dyslipidemia caused by 'Western-diet pattern' is a strong risk factor for the onset of diabetes. This study aimed to disclose the relationship between the serum metabolite changes induced by habitual intake of high-fat and high-cholesterol (HFHC) diet and the development of impaired glucose tolerance (IGT) and insulin resistance through animal models of Macaca mulatta. Sixteen M. mulatta (six months old) were fed a control diet or a HFHC diet for 18 months. The diet effect on serum metabolic profiles was investigated by longitudinal research. Islet function was assessed by intravenous glucose tolerance and hyperinsulinemic-euglycemic clamp test. Metabonomics were determined by (1)H proton nuclear magnetic resonance spectroscopy. Prolonged diet-dependent hyperlipidemia facilitated visceral fat accumulation in liver and skeletal muscle and disorder of glucose homeostasis in juvenile monkeys. Glucose disappearance rate (K(Glu)) and insulin response to the glucose challenge effects in HFHC monkeys were significantly lower than in control monkeys. Otherwise, serum trimethylamine-N-oxide (TMAO), lactate and leucine/isoleucine were significantly higher in HFHC monkeys. Sphingomyelin and choline were the most positively correlated with K(Glu) (R(2) = 0.778), as well as negative correlation (R(2) = 0.64) with total cholesterol. The HFHC diet induced visceral fat, abnormal lipid metabolism and IGT prior to weight gain and body fat content increase in juvenile monkeys. We suggest that increased serum metabolites, such as TMAO, lactate, branched-chain amino acids and decreased sphingomyelin and choline, may serve as possible predictors for the evaluation of IGT and insulin resistance risks in the prediabetic state.
由“西方饮食模式”引起的血脂异常是糖尿病发病的一个强烈危险因素。本研究旨在通过恒河猴动物模型揭示习惯性摄入高脂肪和高胆固醇（HFHC）饮食引起的血清代谢物变化与葡萄糖耐量受损（IGT）和胰岛素抵抗发展之间的关系。16 只猕猴（六个月大）分别喂食对照饮食或 HFHC 饮食 18 个月。通过纵向研究来研究饮食对血清代谢谱的影响。通过静脉葡萄糖耐量和高胰岛素正葡萄糖钳夹试验评估胰岛功能。通过（1）H 质子核磁共振波谱法进行代谢组学研究。依赖饮食的长期高脂血症促进了幼猴肝脏和骨骼肌内脏脂肪的积累以及葡萄糖稳态的紊乱。HFHC 猴子的葡萄糖清除率（K（Glu））和胰岛素对葡萄糖刺激的反应明显低于对照猴子。相反，HFHC 猴子的血清三甲胺 N-氧化物（TMAO）、乳酸和亮氨酸/异亮氨酸明显升高。鞘磷脂和胆碱与 K（Glu）的相关性最强（R（2）=0.778），与总胆固醇呈负相关（R（2）=0.64）。HFHC 饮食导致幼猴内脏脂肪增加、脂质代谢异常和 IGT，然后才出现体重增加和体脂含量增加。我们认为，血清中 TMAO、乳酸、支链氨基酸等代谢物的增加，以及鞘磷脂和胆碱的减少，可能成为评估 IGT 和糖尿病前期胰岛素抵抗风险的潜在预测指标。
