Sex-Specific Differences in Mediobasal Hypothalamus in Response to Nutritional States

Authors

• Jonathan C Bean
• Jinjing Jian
• Tzu-Chiao Lu
• Hailan Liu
• Kristine Conde
• Darah A Threat
• Sanika V Jossy
• Megan E Burt
• Jingjing Cheng
• Yue Deng
• Xing Fang
• Xiaoyu Geng
• Junying Han
• Yongxiang Li
• Hesong Liu
• Qingzhuo Liu
• Yutian Liu
• Yuhan Shi
• Longlong Tu
• Mengjie Wang
• Xu Xu
• Yuxue Yang
• Meng Yu
• Xinming Liu
• Meixin Sun
• Fuhui Wang
• Olivia Z Ginnard
• Yongjie Yang
• Yang He
• Chunmei Wang
• Yanyan Qi
• Hongjie Li
• Yong Xu

Language

English

Publication Date

2-19-2026

Journal

Nature Communications

DOI

10.1038/s41467-026-69239-w

PMID

41714323

PMCID

PMC13031403

PubMedCentral® Posted Date

2-19-2026

PubMedCentral® Full Text Version

Post-print

Abstract

The arcuate nucleus of the hypothalamus plays a central role in sensing and integrating nutritional, hormonal, and neural signals that regulate feeding, energy homeostasis, growth, and reproduction, all of which show pronounced sex differences. However, the cellular mechanisms underlying these responses remain poorly understood. We performed snRNA-seq of the mediobasal hypothalamus, focusing on the arcuate nucleus, in female and male mice under different nutritional states. Analysis of 42 cell types revealed that Agrp neurons were most sensitive to nutritional changes, dopaminergic neurons showed strong sex-specific differences, and KNDy neurons were highly responsive to both sex and nutrition. Pomc neurons displayed moderate nutritional sensitivity. Most glial populations were stable, although microglia and oligodendrocytes showed moderate variation. Cell-cell communication analysis identified neurotrophic factor signaling as a key pathway regulated by sex and nutrition. This study represents a major effort to comprehensively characterize sex-specific differences in arcuate nucleus response across nutritional conditions.

Keywords

Animals, Female, Male, Mice, Arcuate Nucleus of Hypothalamus, Sex Characteristics, Hypothalamus, Mice, Inbred C57BL, Dopaminergic Neurons, Nutritional Status, Agouti-Related Protein, Neurons, Signal Transduction, Pro-Opiomelanocortin, Cell Communication, Neuroglia, Hypothalamus, Feeding behaviour

Published Open-Access

yes

Recommended Citation

Bean, Jonathan C; Jian, Jinjing; Lu, Tzu-Chiao; et al., "Sex-Specific Differences in Mediobasal Hypothalamus in Response to Nutritional States" (2026). Children’s Nutrition Research Center Staff Publications. 363.
https://digitalcommons.library.tmc.edu/staff_pub/363