Aberrant microglial responses shape hypothalamic circuits in anorexia nervosa
- 1Karolinska Institutet
Abstract
Multimodal data indicates that microglia contribute to the pathophysiology of anorexia nervosa (AN). Here, we investigated microglial modulation of hypothalamic circuits, key regulators of energy balance, hypothesising an implication in the prolonged starvation and low body weight of AN. First, we generated microglia as well as hypothalamic and cortical neurons from patient-derived induced pluripotent stem cells (iPSCs) to discover upregulation of synapse-related genes in hypothalamic neurons, reduced microglial uptake of hypothalamic synaptic structures, and a microglial unresponsivness to the satiety hormone glucagon-like peptide-1. In an AN animal model (anx/anx mouse), spatial transcriptomics indicated hypothalamic microglial activation and disrupted microglia-synapse signaling. Despite an increased microglia density in both the arcuate nucleus (ARC) and the dorsomedial hypothalamus region (DMH), microglia displayed a decreased per cell uptake of synaptic material in Arc. Together, these data suggest that microglial responses shape hypothalamic circuits with possible implications for the maintained negative energy balance of AN.
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BibTeX
@misc{xu2026aberrant,
title = {{Aberrant microglial responses shape hypothalamic circuits in anorexia nervosa}},
author = {J. Xu and E. Erskine and B. Eramo and K. Zimmer and C. Camoglio and M. Chaudhary and T. Feng and F. Orhan and E. Welch and L. Selander and C. Lavebratt and T. Hokfelt and M. Schalling and S. S and C. Sellgren-Majkowitz and I. Nilsson},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.18.748216},
url = {https://www.biorxiv.org/content/10.64898/2026.09.18.748216v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Aberrant microglial responses shape hypothalamic circuits in anorexia nervosa
AU - J. Xu
AU - E. Erskine
AU - B. Eramo
AU - K. Zimmer
AU - C. Camoglio
AU - M. Chaudhary
AU - T. Feng
AU - F. Orhan
AU - E. Welch
AU - L. Selander
AU - C. Lavebratt
AU - T. Hokfelt
AU - M. Schalling
AU - S. S
AU - C. Sellgren-Majkowitz
AU - I. Nilsson
PY - 2026
DA - 2026/09/18
PB - bioRxiv
DO - 10.64898/2026.09.18.748216
UR - https://www.biorxiv.org/content/10.64898/2026.09.18.748216v1
AB - Multimodal data indicates that microglia contribute to the pathophysiology of anorexia nervosa (AN). Here, we investigated microglial modulation of hypothalamic circuits, key regulators of energy balance, hypothesising an implication in the prolonged starvation and low body weight of AN. First, we generated microglia as well as hypothalamic and cortical neurons from patient-derived induced pluripotent stem cells (iPSCs) to discover upregulation of synapse-related genes in hypothalamic neurons, reduced microglial uptake of hypothalamic synaptic structures, and a microglial unresponsivness to the satiety hormone glucagon-like peptide-1. In an AN animal model (anx/anx mouse), spatial transcriptomics indicated hypothalamic microglial activation and disrupted microglia-synapse signaling. Despite an increased microglia density in both the arcuate nucleus (ARC) and the dorsomedial hypothalamus region (DMH), microglia displayed a decreased per cell uptake of synaptic material in Arc. Together, these data suggest that microglial responses shape hypothalamic circuits with possible implications for the maintained negative energy balance of AN.
ER -