Induction of ketosis in rats fed low-carbohydrate, high fat diets depends on the relative abundance of dietary fat and protein

Abstract

Low-carbohydrate/high-fat diets (LC-HFDs) in rodent models have been implicated with both weight loss and as therapeutic approach to treat neurological diseases. LC-HFDs are known to induce ketosis, however, systematic studies analyzing the impact of the macronutrient composition on ketosis induction and weight loss success are lacking. Methods: Male Wistar rats were pair-fed either a standard chow diet or one of 3 different LC-HFDs for 4 weeks, which only differed in the relative abundance of fat and protein (percentages of fat/protein in dry matter: LC-75/10; LC-65/20; LC-55/30). We subsequently measured body composition by NMR, analyzed blood chemistry and urine acetone content, evaluated gene expression changes of key ketogenic and gluconeogenic genes, and measured energy expenditure (EE) and locomotor activity (LA) during the first 4 days and after 3 weeks on the respective diets. Results: Compared to chow, rats fed with LC-75/10, LC-65/20 and LC-55/30 gained significantly less bodyweight. Reductions in body weight were mainly due to lower lean body mass and paralleled by significantly increased fat mass. Levels of β-hydroxybutyate were significantly elevated feeding LC-75/10 and LC-65/20 but decreased in parallel to reductions in dietary fat. Acetone was about 16-fold higher with LC-75/10, only (p