The Effect of Nutritional Ketosis on Aquaporin Expression in Apolipoprotein E-Deficient Mice: Potential Implications for Energy Homeostasis

Abstract

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 ApoE−/− (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 Aqp7 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.