Initiation and perpetuation of obesity and obesity resistance in rats.

A search was made for predisposing factors and sequelae of diet-induced obesity (DIO) or resistance to DIO (DR). During 3 mo on a high-energy (CM) diet, two-thirds of the male Sprague-Dawley rats ate 16% more calories over the first 30 days and developed DIO. The remaining one-third were DR, gaining the same amount of weight as chow-fed controls. Basal and norepinephrine (NE)-stimulated in vivo O2 consumption, performed before rats were placed on the CM diet, was the same in those rats that later became DR or DIO after 3 mo on the CM diet. DR rats were 4% lighter, whereas DIO rats were equal to chow-fed rats before their exposure to the CM diet. When CM-fed rats were switched to chow, DIO rats took 14 wk to reduce their body and retroperitoneal fat pad weights to those of chow-fed controls, whereas DR rats gained only 40% of the body weight, and fat pads were 34% lighter than controls. After 14 wk, DIO rats were neither hyperinsulinemic nor insulin resistant, whereas DR rats had 64% reduced areas under their insulin curves after intravenous glucose (1 g/kg) compared with controls. Unlike younger rats, animals here had inconsistent plasma NE responses to intravenous glucose. Therefore the CM diet produces DR and DIO states that tend to become self-perpetuating once established.