Neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (
ARC) produce metabolic and physiological effects that promote the development and maintenance of
obesity. In turn, NPY metabolism in these neurons is inhibited by
dopamine release. In this study,
ARC prepro-NPY mRNA and
ARC/median eminence (ME)
dopamine turnover were assessed in chow-fed male Sprague-Dawley rats prone to develop diet-induced
obesity (DIO) or to be diet resistant (DR) when fed a high-energy (HE) diet. By in situ hybridization, DIO-prone rats had 39% more
ARC NPY
mRNA expression than DR-prone rats under chow-fed conditions. DIO-prone rat
ARC/ME
dopamine levels were 14% higher, but
dopamine half-life was 176% longer and turnover was 59% less than DR-prone rats. Neither a 48-h fast nor 50% energy intake restriction for 5 days affected the already increased
ARC NPY
mRNA levels in DIO-prone rats. Both manipulations increased NPY expression to the level of DIO-prone rats in DR-prone rats by 23 and 35%, respectively. Finally, when fed HE diet for 2 wk, neither DIO- nor DR-prone rats altered their
ARC NPY expression despite the development of
obesity and
hyperinsulinemia in DIO rats. Thus DIO-prone rats overexpress and fail to regulate
ARC NPY
mRNA to energy restriction or
hyperinsulinemia. This dysregulation is possibly secondary to reduced inhibition because of defective
ARC/ME
dopamine turnover. Both may be important predisposing factors in the development of DIO.