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Am J Physiol Regul Integr Comp Physiol 283: R941-R948, 2002; doi:10.1152/ajpregu.00245.2002
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Vol. 283, Issue 4, R941-R948, October 2002

Reduced central leptin sensitivity in rats with diet-induced obesity

Barry E. Levin and Ambrose A. Dunn-Meynell

Neurology Service (127C), Department of Veterans Affairs Medical Center, East Orange 07018; and Department of Neurosciences, New Jersey Medical School, Newark, New Jersey 07103

On low-fat chow diet, rats prone to diet-induced obesity (DIO) have increased arcuate nucleus neuropeptide Y (NPY) expression but similar leptin levels compared with diet-resistant (DR) rats (19). Here, body weight and leptin levels rose in DIO rats, and they defended their higher body weight after only 1 wk on a 31% fat high-energy (HE) diet. However, DIO NPY expression did not fall to DR levels until 4 wk when plasma leptin was 168% of DR levels. When switched to chow, DIO rats lost carcass fat (18). By 10 wk, leptin levels fell to 148% and NPY expression again rose to 150% of DR levels. During 4 wk of food restriction, DIO leptin fell by ~50% while NPY increased by 30%. While both returned to control levels by 8 wk, DIO rats still regained all lost weight when fed ad libitum. Finally, the anorexic effect of intracerebroventricular leptin (10 µg) was inversely correlated with subsequent 3-wk weight gain on HE diet. Thus NPY expression and food intake are less sensitive to the leptin's suppressive effects in DIO rats. While this may predispose them to develop DIO, it does not fully explain their defense of a higher body weight on HE diet.

neuropeptide Y; food intake; arcuate nucleus; leptin resistance


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