The undeveloped properties of GABA neurons in the ventral tegmental area promote energy intake for growth in juvenile rats

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.

Early life high-fat diet exposure evokes normal weight obesity

“…As for the energy intake, the HFD adult group showed higher energy intake from the beginning of HFD feeding. This corresponds to the previous studies showing energy intake being significantly higher in HFD fed rats, compared NCD fed rats for the first five to 6 days and then decrease [7,15]. HFD is a highly palatable food and known to stimulate reward related area, such as ventral tegmental area (VTA) of the brain.…”

“…However, even with the same caloric intake, HFD is known to induce significantly higher BW increase compared to NCD in adult rats [23]. Our previous study revealed that HFD feeding increases locomotor activity via undeveloped properties of GABA neurons in VTA and decreases inhibitory input to dopamine neurons leading to hyperactivity of dopamine neurons in the VTA of juvenile rats [7]. Thus, fact that there were no differences in BW between HFD and NCD fed juvenile rats in the current study may be explained by increasing energy expenditure following increased locomotor activity.…”

“…This is maybe due to the immaturity of GABAnergic neurons in VTA of juvenile rats. Our previous study revealed that the hyperactivity of dopamine neurons in VTA of juvenile rat compared with that of adults were induced by the undeveloped properties of GABA neurons which resulted in less inhibitory input to dopamine neurons [7]. This is considered as an underlying mechanism for juvenile rats to induce maximum energy intake regardless of HFD or NCD in order to promote growth [7].…”

“…The modern lifestyle is characterized by a lack of physical activity and excessive energy intake from high caloric diet in both children and adults. In the juvenile stage, animals, including human, are in a dramatic growth period and have very different energy metabolism and feeding regulations compared to adult animals [7]. In our previous study, we showed that neurons in the ventral tegmental area that regulate feeding and energy metabolism show undeveloped properties in weaning rats [7].…”

“…In the juvenile stage, animals, including human, are in a dramatic growth period and have very different energy metabolism and feeding regulations compared to adult animals [7]. In our previous study, we showed that neurons in the ventral tegmental area that regulate feeding and energy metabolism show undeveloped properties in weaning rats [7]. Thus, it can be considered that juvenile animals, which are in a dramatic growth period, are easily influenced by the balance of nutrition.…”