Dietary Effects Of The High Fat Ketogenic And High Protein Ketogenic Diets In Obese And Lean Zucker Rats

Abstract

We developed two different ketogenic diets, which will allow us to understand the mechanisms of ketosis in lean and obese female and male Zucker rats. The obese Zucker rat has a point mutation in the long form of the leptin receptor causing these rats to be refractory to endogenous leptin, hyperinsulinemic, and obese (perhaps analogous to some states of human obesity). Leptin is currently believed to control body composition largely via hypothalamic receptors that regulate food intake and thermogenesis. In this study, 50 lean and obese female Zucker rats and 48 lean and obese male Zucker rats were offered ad libitum three different diets. A high protein (50% casein by calories, 43% hydrogenated fat, 7% polyunsaturated, no carbohydrate ketogenic diet), a high fat (76% hydrogenated fat, 13% polyunsaturated fat, 11% casein, no carbohydrate ketogenic diet), and AIN93-G, a normal rat chow (all diets provided the required vitamins and minerals for normal growth and maintenance for rats). Food intake and body weights were recorded every other day. Animals were placed in respiration chambers where oxygen consumption, carbon dioxide production, and heat production were recorded for 48 hours. There was a statistically significant difference (p<0.5) in oxygen consumption, respiratory quotient, and heat production per metabolic body size between the different diets and among the different phenotypes (p<0.5) but male and female rats responded similarly. Animals were tested for serum levels of beta-hydroxybutyrate to establish ketosis and to correlate with respiration trial data obtained using the respiration chambers. Weight gain over time was lessened in the obese Zucker on the high protein ketogenic diet, whereas weight gain was attenuated in the lean Zucker rat on the high-fat ketogenic diet. Circulating levels of triglycerides, leptin, and insulin were measured as well as fat pad weights. Results indicate that there is a differential phenotypic response to the ketogenic diets.