Short-term effects of a ketogenic diet on bodyweight development and metabolic hormones in young and older rodents

Abstract

Ketogenic diets (KD) are demonstrated to be effective in reducing body weight and are often used for the treatment of intractable epilepsy in children. The current investigation was designed to investigate the response of consuming a KD on bodyweight and metabolic hormones in young (n=16; 335±6.9g) and older (n=16; 432±5.97g) male Wistar rats. Animals were maintained on either laboratory chow (CH n=16, 8/age group) or ketogenic diet (KD n=16, 8/age group). Animals were pair fed to ensure that energy intake was identical between groups. At the end of the 16d intervention all animals were fasted for 6 hours before decapitation and collection of truncal blood. At the end of the 16d, animals on KD were lighter in both age groups. Younger rats maintained on CH gained more body weight (61.85±5.46g) than the older animals (49.12±2.62; p=0.054). Yet there were no significant differences were found in the animals maintained on KD (young -1.98±3.29g, older -0.47g±2.69; p>0.05). Plasma protein was significantly lower in the KD animals (5.4±0.08g/dl) in comparison to the CH group (5.69±0.08g/d; p=0.01) with the young KD animals having the lowest levels. Consuming the KD resulted in higher triglycerides (TAG 246.58±15.8mg/dl versus 71.85±15.3mg/dl). Older KD animals had higher TAG levels in comparison to older CH animals, yet no differences were found between the younger groups. Insulin was lower in the KD animals (0.28±0.06ng/ml versus 0.6±0.06, p=0.001). Growth hormone was decreased in the KD group (257.82±253.78 versus 984.53±245.17ng/ml, p=0.049) as was IGF-I (1903.67±68.41 versus 1627.77±65.91ng/ml; p=0.008). Leptin was significantly elevated in the KD group (3.44±0.28 versus 1.27±0.35ng/ml, p=0.0001). In summary, short-term exposure to a KD results in less weight gain in both young and old animals. The observed effects on protein and metabolic hormones suggest profound detrimental effects on development or maintenance of lean body tissue. Implications of these findings pertain to the administration of such diets for weight loss and intractable epilepsy in children.