Abstract
Juvenile animals show higher energy intake (EI) per body weight (BW) to meet the energy requirements for growth. However, the underlying mechanisms that induce high EI/BW in juvenile animals remain unknown. The EI from a control diet (CD) and high fat diet (HFD), as well as BW changes were compared between juvenile (3 weeks old) and adult (8 weeks old) rats. BW gain and EI were increased in the HFD-fed adult rats compared to the CD-fed adult rats. However, in the juvenile rats, there were no differences in BW gain and EI between the CD-fed and HFD-fed groups. The locomotor activity was significantly increased in HFD group compared with the CD group in juvenile, but not in adult rats. Gamma-aminobutyric acid (GABA) neurons in the VTA were found to remain undeveloped with less GABAergic input into dopamine neurons in the juvenile rats. The deletion of the VTA GABA neurons in the adult rats significantly increased CD consumption, but showed almost no change in HFD consumption. These data suggest that undeveloped properties of VTA GABA neurons in juvenile rats can promote higher EI regardless of high or less palatable feeding, and contribute to growth promotion.
Highlights
The neonatal and juvenile periods are critical stages of development during the growth stage[1,2,3]
In eight-week-old adult rats, body weight (BW) gain and energy intake (EI) were significantly increased under high fat diet (HFD) conditions (BW; F1,65 = 118.54, P < 0.01, EI; F1,65 = 144.17, P < 0.01, Fig. 1c) compared with a control diet (CD) (Fig. 1d,e)
In three-week-old juvenile rats, there was no difference in BW gain or EI between the CD- and HFD-fed rats (BW; F1,70 = 0.135, P > 0.05, EI; F1,70 = 0.076, P > 0.05, Fig. 1g–i)
Summary
The neonatal and juvenile periods are critical stages of development during the growth stage[1,2,3]. One is homeostatic food intake and the other is hedonic/reward food intake These two mechanisms are regulated in two different areas of the brain, the hypothalamus and limbic system[4,5]. The ventral tegmental area (VTA) dopamine neurons are known critical mediators in food reward[10], and the projection from dopamine neurons to the nucleus accumbens (NAc) promote the initiation and maintenance of reward seeking and consumption[9,10,11]. The properties of the hypothalamus and limbic pathway at the juvenile stage are reported to be different compared to those of adults. As for the limbic pathway, a previous study showed that anorexigenic adipocytokine, leptin, which is reported to reduce the firing rate of VTA dopamine neurons in adult rats, failed to increase leptin signaling in www.nature.com/scientificreports/
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