SK3 in POMC Neurons Plays a Sexually Dimorphic Role in Energy and Glucose Homeostasis

Authors

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

Publication Date

10-9-2022

Journal

Cell & Bioscience

DOI

10.1186/s13578-022-00907-2

PMID

36210455

PMCID

PMC9549684

PubMedCentral® Posted Date

10-9-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

POMC neurons, SK current, Sexually dimorphism, Energy and glucose homeostasis

Abstract

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.