A controlled high-fat diet induces an obese syndrome in rats

The prevalence of obesity is increasing. Although the etiology of obesity is complex, dietary factors, particularly the consumption of a high-fat (HF) diet, is considered a risk factor for its development. Nonetheless, a causal role of dietary fat has never been definitively documented, in part because of inadequate animal models. We developed a rat model of diet-induced obesity that will be a powerful tool for assessment of this issue. In four experiments, Long-Evans rats ate ad libitum a synthetic semipurified diet containing 20 g (HF) or 4 g [low-fat (LF)] of fat/100 g of diet or a nonpurified diet. Other rats ate ad libitum the HF diet in amounts matched to the energy intake of the LF rats. When compared over 10 wk of free feeding, HF rats weighed 10% more (P < 0.01) than LF rats and had 50% more body fat (P < 0.01), as well as significant hyperleptinemia and insulin resistance. Compared with rats fed the nonpurified diet, the HF rats had even more marked differences in these variables. The rats fed the HF diet to match the rats fed the LF diet had similar body weights but significantly more adipose tissue than LF rats, suggesting that diet composition and/or energy density of the diet affects fat deposition. This dietary regimen has reproducible effects on body size and composition, and these are similar in male and female rats. This model of diet-induced obesity will be a useful tool for studying the mechanisms by which dietary fat influences the regulation of energy balance.