# Modulation of the association between blood glucose homeostasis and social hierarchy among co-housed mice by diet and amygdala activities

**Authors:** Rikako Ukichi, Yukari Takahashi, Momoyo Ibukuro, Yae K. Sugimura, Keiichiro Matoba, Rimei Nishimura, Fusao Kato

PMC · DOI: 10.1016/j.jphyss.2026.100058 · 2026-01-20

## TL;DR

This study shows that diet and amygdala activity can influence how social rank affects blood sugar control in mice.

## Contribution

The study reveals a novel link between social hierarchy, diet, and glucose regulation through amygdala modulation in mice.

## Key findings

- High-fat diets disrupted social hierarchies and altered glucose homeostasis in mice.
- Amygdala inhibition in low-ranking mice changed both their glucose regulation and that of their cage-mates.
- Rapid glucose responses and pancreatic islet size were influenced by social rank.

## Abstract

Recent clinical studies suggest that individual psychosocial traits play a significant role in the onset and progression of diabetes. To examine whether glucose homeostasis depends on the social rank of individual mice, we analyzed the effects of dietary fat content on the hierarchy formed among co-housed mice and evaluated how perturbing rank by inhibiting amygdala neuronal activity influences glucose regulation. Social rank among four co-housed mice was assessed using the tube test. Switching to a high-fat diet altered blood glucose homeostasis, particularly by affecting rapid responses, and disrupted the established hierarchy, with the degree of disruption varying according to each mouse’s rank. In contrast, chemogenetic inhibition of neuronal activities in the basolateral amygdala and surrounding area in the lowest-ranking mice modified both glucose homeostasis and its association with social rank. These findings provide mechanistic insight into the interaction between glucose regulation and psychosocial status.

•Glucose metabolism traits of co-caged mice were associated with individual social rank.•Dietary fat content changes disrupted established social rank and glucose metabolism.•Rapid glucose responses and pancreatic islet size depended on individual social rank.•Rapid glucose responses were associated with the social rank of individual mice.•Inhibiting amygdala neurons in subordinate mice altered cage-mates’ glucose metabolism.

Glucose metabolism traits of co-caged mice were associated with individual social rank.

Dietary fat content changes disrupted established social rank and glucose metabolism.

Rapid glucose responses and pancreatic islet size depended on individual social rank.

Rapid glucose responses were associated with the social rank of individual mice.

Inhibiting amygdala neurons in subordinate mice altered cage-mates’ glucose metabolism.

## Linked entities

- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Agrp (agouti related neuropeptide) [NCBI Gene 11604] {aka Agrt, Art}, Camk2a (calcium/calmodulin-dependent protein kinase II alpha) [NCBI Gene 12322] {aka CaMKII, mKIAA0968}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064]
- **Diseases:** adrenal hyperplasia (MESH:D000312), inflammation (MESH:D007249), dislocation (MESH:D004204), Pain (MESH:D010146), bodily injury (MESH:D009440), depression (MESH:D003866), impaired spatial memory (MESH:D008569), insulin resistance (MESH:D007333), Diabetes mellitus (MESH:D003920), type 2 diabetes (MESH:D003924), PTSD (MESH:D013313), aggression (MESH:D010554), hyperglycemia (MESH:D006943), autonomic (MESH:D001342), hyperphagia (MESH:D006963)
- **Chemicals:** water (MESH:D014867), Saline (MESH:D012965), paraffin (MESH:D010232), clozapine (MESH:D003024), Blood glucose (MESH:D001786), hematoxylin (MESH:D006416), insulin (MESH:D007328), sodium pentobarbital (MESH:D010424), carbohydrate (MESH:D002241), eosin (MESH:D004801), sucrose (MESH:D013395), CNO (MESH:C079149), H&amp;E (MESH:D006371), paraformaldehyde (MESH:C003043), phosphate (MESH:D010710), ethanol (MESH:D000431), corticosterone (MESH:D003345), fat (MESH:D005223), butorphanol tartrate (MESH:D002077), midazolam (MESH:D008874), Deltaglucose (-), Glucose (MESH:D005947), medetomidine hydrochloride (MESH:D020926)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Mutations:** V10001C
- **Cell lines:** hM4Di — Rattus norvegicus (Rat), Hybridoma (CVCL_A5ZQ), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12870758/full.md

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Source: https://tomesphere.com/paper/PMC12870758