da Silva Inês V, Gullette Sean, Florindo Cristina, Huang Neil K, Neuberger Thomas, Ross A Catharine, Soveral Graça, Castro Rita
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
Biomedicines. 2022 May 18;10(5):1159. doi: 10.3390/biomedicines10051159.
Ketogenic diets (KDs) are very low-carbohydrate, very high-fat diets which promote nutritional ketosis and impact energetic metabolism. Aquaporins (AQPs) are transmembrane channels that facilitate water and glycerol transport across cell membranes and are critical players in energy homeostasis. Altered AQP expression or function impacts fat accumulation and related comorbidities, such as the metabolic syndrome. Here, we sought to determine whether nutritional ketosis impacts AQPs expression in the context of an atherogenic model. To do this, we fed (apolipoprotein E-deficient) mice, a model of human atherosclerosis, a KD (Kcal%: 1/81/18, carbohydrate/fat/protein) or a control diet (Kcal%: 70/11/18, carbohydrate/fat/protein) for 12 weeks. Plasma was collected for biochemical analysis. Upon euthanasia, livers, white adipose tissue (WAT), and brown adipose tissue (BAT) were used for gene expression studies. Mice fed the KD and control diets exhibited similar body weights, despite the profoundly different fat contents in the two diets. Moreover, KD-fed mice developed nutritional ketosis and showed increased expression of thermogenic genes in BAT. Additionally, these mice presented an increase in Aqp9 transcripts in BAT, but not in WAT, which suggests the participation of Aqp9 in the influx of excess plasma glycerol to fuel thermogenesis, while the up-regulation of in the liver suggests the involvement of this aquaporin in glycerol influx into hepatocytes. The relationship between nutritional ketosis, energy homeostasis, and the AQP network demands further investigation.
生酮饮食（KDs）是碳水化合物含量极低、脂肪含量极高的饮食，可促进营养性酮症并影响能量代谢。水通道蛋白（AQPs）是跨膜通道，可促进水和甘油跨细胞膜运输，是能量稳态的关键参与者。AQP表达或功能的改变会影响脂肪堆积及相关合并症，如代谢综合征。在此，我们试图确定在动脉粥样硬化模型背景下营养性酮症是否会影响AQP的表达。为此，我们给载脂蛋白E缺陷小鼠（一种人类动脉粥样硬化模型）喂食KD（热量百分比：1/81/18，碳水化合物/脂肪/蛋白质）或对照饮食（热量百分比：70/11/18，碳水化合物/脂肪/蛋白质）12周。收集血浆进行生化分析。安乐死后，取肝脏、白色脂肪组织（WAT）和棕色脂肪组织（BAT）进行基因表达研究。尽管两种饮食中的脂肪含量差异很大，但喂食KD和对照饮食的小鼠体重相似。此外，喂食KD的小鼠出现了营养性酮症，且BAT中产热基因的表达增加。此外，这些小鼠BAT中Aqp9转录本增加，但WAT中未增加，这表明Aqp9参与了多余血浆甘油的流入以促进产热，而肝脏中该蛋白的上调表明该水通道蛋白参与了甘油流入肝细胞的过程。营养性酮症、能量稳态和AQP网络之间的关系需要进一步研究。
