Consumption of a high-fat diet alters the homeostatic regulation of energy balance

Humans in many countries are currently experiencing what has been called an epidemic of obesity. That is, the average body weight (and amount of fat stored in the body) is increasing over years, carrying with it a multitude of associated medical, psychological, and economic problems. While there is no shortage of possible causes of this epidemic, increased availability and consumption of high-fat (HF), calorically dense and generally quite palatable food is often touted as a likely culprit. In order to better assess the impact of consuming a diet with those qualities, we have developed a well-controlled animal model in which the effects of chronic consumption of a high-fat diet can be dissociated from those of becoming obese per se. Long-Evans rats are fed one of two semipurified pelleted diets, a HF diet that contains 20% fat by weight and a low-fat (LF) diet that contains 4% fat by weight. Pair-fed animals consume the HF diet but are limited to the daily caloric intake of LF rats. Another group receives pelleted chow. Relative to animals consuming diets low in fat, HF animals weigh more, have more carcass fat, are hyperinsulinemic and hyperleptinemic, and are insulin resistant. HF-fed animals, independent of whether they become obese or not, also have central insulin and MTII insensitivity. Finally, HF rats have a down-regulated hypothalamic apo A-IN system that could contribute to their hyperphagia. (C) 2004 Elsevier Inc. All rights reserved.