Restricting energy expenditure is an adaptive response to food shortage. Despite being insulated with massive amount of fat tissues,
leptin-deficient mice lose the ability to maintain their body temperature and develop deep
hypothermia, which can be suppressed by exogenous
leptin, suggesting an important role for
leptin in energy expenditure regulation. However, the mechanism underlying the
leptin action is not clear. We generated mice with disruption of
glutamate release from
leptin receptor-expressing neurons by deleting
vesicular glutamate transporter 2 in these neurons, and found that these mice developed mild
obesity purely due to reduced energy expenditure, exhibited bouts of rapidly reduced energy expenditure, body temperature and locomotion. In addition, these mice exhibited lower energy expenditure and body temperature in response to fasting and were defective in
leptin-mediated thermogenic action in brown adipose tissues. Taken together, our results identify a role for
glutamate release in mediating
leptin action on energy expenditure.