|Induction of ketosis in rats fed low-carbohydrate, high fat diets depends on the relative abundance of dietary fat and protein. |
Bielohuby, Maximilian, et al.
American journal of physiology. Endocrinology and metabolism, (2010)
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<0.001). In contrast, rats fed with LC-55/30 were not ketotic. Serum FGF-21, hepatic mRNA expression of hydroxymethylglutaryl-CoA-lyase, PGC-1α and PGC-1β were increased with LC-75/10, only. Expression of PCK1 and glucose-6-phosphatase was down-regulated by 50-70% in LC-HF groups. Furthermore, EE and LA were significantly decreased in all groups fed with LC-HFDs after 3 weeks on the diets. Summary: In rats, the absence of dietary carbohydrates per se does not induce ketosis. LC-HFDs must be high in fat, but also low in protein contents to be clearly ketogenic. Independent of the macronutrient composition, LC-HFD-induced weight loss is not due to increased EE and LA.