Ferenc Karolina, Marcinkowski Michał, Olszewski Jarosław, Kowalczyk Paweł, Pilžys Tomaš, Garbicz Damian, Dib Naser, Świderska Bianka, Matyba Piotr, Gajewski Zdzisław, Grzesiuk Elżbieta, Zabielski Romuald
Center for Translational Medicine, Warsaw University of Life Sciences, Nowoursynowska 100, 02-797, Warsaw, Poland.
Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawińskiego 5a, 02-106, Warsaw, Poland.
Sci Rep. 2024 May 3;14(1):10235. doi: 10.1038/s41598-024-60022-9.
To reveal the sources of obesity and type 2 diabetes (T2D) in humans, animal models, mainly rodents, have been used. Here, we propose a pig model of T2D. Weaned piglets were fed high fat/high sugar diet suppling 150% of metabolizable energy. Measurements of weight gain, blood morphology, glucose plasma levels, cholesterol, and triglycerides, as well as glucose tolerance (oral glucose tolerance test, OGTT) were employed to observe T2D development. The histology and mass spectrometry analyses were made post mortem. Within 6 months, the high fat-high sugar (HFHS) fed pigs showed gradual and significant increase in plasma triglycerides and glucose levels in comparison to the controls. Using OGTT test, we found stable glucose intolerance in 10 out of 14 HFHS pigs. Mass spectrometry analysis indicated significant changes in 330 proteins in the intestine, liver, and pancreas of the HFHS pigs. These pigs showed also an increase in DNA base modifications and elevated level of the ALKBH proteins in the tissues. Six diabetic HFHS pigs underwent Scopinaro bariatric surgery restoring glycaemia one month after surgery. In conclusion, a high energy diet applied to piglets resulted in the development of hyperlipidaemia, hyperglycaemia, and type 2 diabetes being reversed by a bariatric procedure, excluding the proteomic profile utill one month after the surgery.
为了揭示人类肥胖和2型糖尿病(T2D)的病因,人们使用了动物模型,主要是啮齿动物。在此,我们提出一种T2D猪模型。给断奶仔猪喂食提供150%可代谢能量的高脂肪/高糖饮食。通过测量体重增加、血液形态、血糖水平、胆固醇和甘油三酯,以及葡萄糖耐量(口服葡萄糖耐量试验,OGTT)来观察T2D的发展。死后进行组织学和质谱分析。在6个月内,与对照组相比,喂食高脂肪高糖(HFHS)的猪血浆甘油三酯和葡萄糖水平逐渐显著升高。使用OGTT试验,我们发现14只HFHS猪中有10只存在稳定的葡萄糖不耐受。质谱分析表明,HFHS猪的肠道、肝脏和胰腺中有330种蛋白质发生了显著变化。这些猪的组织中DNA碱基修饰也增加,ALKBH蛋白水平升高。6只糖尿病HFHS猪接受了斯科皮纳罗减肥手术,术后1个月血糖恢复正常。总之,给仔猪喂食高能量饮食会导致高脂血症、高血糖症和2型糖尿病的发生,减肥手术可逆转这些症状,但术后1个月内蛋白质组学特征除外。