Journal Article

SK3 in POMC neurons plays a sexually dimorphic role in energy and glucose homeostasis

Li, Yongxiang, Scarcelli, Nikolas A., Cai, Xing, Xu, Yong, Zhang, Nan, Xu, Pingwen, Yang, Yongjie, Bean, Jonathan C., Tu, Longlong, He, Yanlin, Conde, Kristine M., Wang, Chunmei, Han, Junying, Pei, Zhou, Liu, Hesong, Wang, Mengjie, Yu, Kaifan, Liu, Hailan, He, Yang, Yu, Meng, Yin, Na

2022

Overview

Background Pro-opiomelanocortin (POMC) neurons play a sexually dimorphic role in body weight and glucose balance. However, the mechanisms for the sex differences in POMC neuron functions are not fully understood. Results We detected small conductance calcium-activated potassium (SK) current in POMC neurons. Secondary analysis of published single-cell RNA-Seq data showed that POMC neurons abundantly express SK3, one SK channel subunit. To test whether SK3 in POMC neurons regulates POMC neuron functions on energy and glucose homeostasis, we used a Cre-loxP strategy to delete SK3 specifically from mature POMC neurons. POMC-specific deletion of SK3 did not affect body weight in either male or female mice. Interestingly, male mutant mice showed not only decreased food intake but also decreased physical activity, resulting in unchanged body weight. Further, POMC-specific SK3 deficiency impaired glucose balance specifically in female mice but not in male mice. Finally, no sex differences were detected in the expression of SK3 and SK current in total POMC neurons. However, we found higher SK current but lower SK3 positive neuron population in male POMC neurons co-expressing estrogen receptor α (ERα) compared to that in females. Conclusion These results revealed a sexually dimorphic role of SK3 in POMC neurons in both energy and glucose homeostasis independent of body weight control, which was associated with the sex difference of SK current in a subpopulation of POMC + ERα + neurons.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Animals / Biomedical and Life Sciences / Body weight / Calcium conductance / Cell Biology / Dextrose / Energy / Energy and glucose homeostasis / Estrogen / Estrogen receptors / Exercise / Food intake / Gender differences / Gene expression / Glucose / Homeostasis / Hypothalamus / Insulin / Kinases / Laboratories / Life Sciences / Metabolism / Microbiology / Neurobiology / Neurons / Obesity / Physical activity / POMC neurons / Potassium / Potassium channels (calcium-gated) / Potassium conductance / Proopiomelanocortin / Proteomics / RNA sequencing / Rodents / Sex differences / Sexual dimorphism / Sexually dimorphism / SK current / Stem Cells