Long-Term Metabolic and Health Effects of a Low-Carbohydrate, High-Fat, High-Protein Diet in Mus musculus: a Nineteen Week Longitudinal Study

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This study was designed to investigate the long-term metabolic adaptations and health effects of a low-carbohydrate, high-fat/protein diet in mice. One month old male ICR mice were fed a control, conventional high-carbohydrate diet (n!) or an experimental low-carbohydrate, high-fat, high-protein diet (n ). One pair of mice per group was euthanized at two week intervals for five months for tissue analysis. Basic metabolic data, body and tissue weights, blood and plasma metabolite and lipid profiles, liver glycogen and protein content, and liver serine dehydratase and glucose-6-phosphate dehydrogenase activities were analyzed. The low-carbohydrate group gained significantly more weight (p<0.005 after 4 weeks) than the normally growing control group. Although ketosis was initially stimulated in the low-carbohydrate group, enzyme and tissue analysis suggest gluconeogenic activity was sufficient to alleviate the effects of severe dietary carbohydrate restriction and allow for glucose metabolism close to that demonstrated in the control group.