Pro-opiomelanocortin (POMC) neurons are important for body weight and glucose balance. The inhibitory tone to POMC neurons is mediated primarily by GABA receptor complex. However, the detailed mechanisms and functions of GABA receptors are not well understood. We found that α5 subunit of GABA receptor complex, Gabra5, is highly expressed in POMC neurons. To explore the function of Gabra5 in POMC neurons, we deleted Gabra5 specifically from mature POMC neurons using the CRISPR-Cas9 strategy. Body weight and food intake were not affected in either male mice or female mice by the deletion of Gabra5 from POMC neurons. We found that the deletion of Gabra5 caused a significant increase in the firing frequency and rest membrane potential, and a decrease in the amplitude of mIPSC in male POMC neurons. However, the deletion of Gabra5 just modestly decreased the frequency of mIPSC in female POMC neurons. Consistently, loss of Gabra5 from POMC neurons significantly improved the glucose tolerance in male mice but not in female mice. These results revealed a sexually dimorphic role of Gabra5 in POMC neuron activity and glucose balance, independent of body weight control.
Z.Pei: None. Y.He: None. Y.He: None. Y.Xu: None. C.Wang: None.
National Institutes of Health (KDK119471)