ESPE Abstracts

Objectives: To test whether Gabra5 in POMC neurons regulates energy balance and glucose metabolism in sexually dimorphic fashion.

Methods: POMC-Cre mice received stereotaxic injections of AAV-FLEX-scCAS9 and AAV-FLEX-Gabra5-sgRNA-tdTOMATO into ARH to generate pomc-Gabra5 KO mice. Both male and female mice were fed on regular chow diet or HFD. Food intake, body weight and anal temperature were measured every 4 days. Fat/lean mass were measured by QMR. Glucose tolerance test and insulin tolerance test were done before and after HFD feeding. Glucose clamp was also done after 4 weeks HFD feeding.

Results: Neither on chow diet nor HFD, no significant difference was found in food intake, body weight and anal temperature in males and females compared with their controls. Female Gabra5-KO mice on HFD showed impaired insulin tolerance. While male Gabra5-KO mice on HFD showed improved insulin tolerance.

Conclusions: Specific deletion of Gabra5 in POMC neuron doesn't relate to energy expenditure neither in males nor females. However, pomc-Gabra5 KO could improve glucose tolerance only in male mice, while female mice showed opposite result. These results provide evidence for sex differences in glucose metabolism.