School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia.
School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.
Biosci Rep. 2018 Dec 14;38(6). doi: 10.1042/BSR20181873. Print 2018 Dec 21.
Postnatal overconsumption of fat is believed to increase the susceptibility to metabolic disease in the later life. Here we examined whether prior exposure to high fat (HF) in the adulthood may also accelerate the development of metabolic disorders in mice. Adult mice (12 weeks) were pre-exposed to two episodes of an HF diet each for 2 weeks followed by 2 weeks of washout with a low-fat diet. The mice were then fed the same HF diet for 6 weeks. Unexpectedly, prior exposures to HF diet significantly alleviated body weight gain, visceral adiposity and glucose/insulin intolerance during the period of last HF feeding. These protective effects were evident without changing calorie intake and were specific for HF, but not high fructose (HFru) diet. Following the HF prior exposures was increases in plasma fibroblast growth factor 21 (FGF21), the expressions of phospho-AMP-activated protein kinase (pAMPK), mitochondrial complex II and the expression of uncoupling protein (UCP) 3 in muscle and UCP1 and Sirtuin 1 (SIRT1) in adipose tissue. However, in the liver there was no significant change in pAMPK, SIRT1 expression or the capacity of glucose production. These findings indicated that, instead of exacerbating metabolic conditions, prior exposures to HF diet lead to the preconditioning against subsequent overload of HF, possibly involving FGF21-associated enhancement of markers for metabolic capacity in muscle and adipose tissue. This paradoxical phenomenon may offer a unique paradigm to identify factors and explore dietary ingredients with beneficial effects for the control of the metabolic syndrome in humans.
人们普遍认为，产后脂肪摄入过多会增加晚年患代谢疾病的易感性。在这里，我们研究了成年期之前暴露于高脂肪（HF）是否也会加速小鼠代谢紊乱的发展。成年小鼠（12 周龄）先经历两次为期 2 周的 HF 饮食暴露，然后用低脂饮食洗脱 2 周。然后，这些小鼠再喂食相同的 HF 饮食 6 周。出乎意料的是，HF 饮食的预先暴露显著减轻了最后 HF 喂养期间的体重增加、内脏脂肪堆积和葡萄糖/胰岛素不耐受。这些保护作用在不改变热量摄入的情况下是明显的，并且是 HF 特异性的，而不是高果糖（HFru）饮食特异性的。HF 预先暴露后，血浆成纤维细胞生长因子 21（FGF21）、磷酸化 AMP 激活蛋白激酶（pAMPK）、线粒体复合物 II 的表达以及肌肉中的解偶联蛋白 3（UCP3）和脂肪组织中的 UCP1 和 Sirtuin 1（SIRT1）的表达增加。然而，肝脏中 pAMPK、SIRT1 表达或葡萄糖生成能力没有显著变化。这些发现表明，HF 饮食的预先暴露并没有加剧代谢状况，而是导致对随后 HF 过载的预处理，可能涉及 FGF21 相关的增强肌肉和脂肪组织代谢能力的标志物。这种矛盾的现象可能为确定因素和探索具有人类代谢综合征控制有益效果的饮食成分提供了一个独特的范例。
