PuSH - Publication Server of Helmholtz Zentrum München: Low-to-moderate dosed cranial irradiation in young mice induces sex-specific metabolic disturbances later in life.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Harrison, L. ; Schriever, S.C. ; Bernecker, M. ; Mallet, N. ; Mencias Castillejo, C. ; Ameli, H. ; Baumann, P. ; Contreras, R. ; Stolz, J. ; Lindner, R. ; Bartzsch, S. ; Schmid, T.E. ; Combs, S.E. ; Rosemann, M. ; Pfluger, P.T.

Low-to-moderate dosed cranial irradiation in young mice induces sex-specific metabolic disturbances later in life.

Diabetes 74, 1775-1786 (2025)

DOI

PMC

Open Access Green as soon as Postprint is submitted to ZB.

Abstract
Metrics
Extra information

UNLABELLED: Survivors of childhood cancers who received high doses (40-60 Gy) of cranial irradiation (CI) have increased risks of developing obesity, type 2 diabetes, and metabolic syndrome (MetS). Here, we subjected mice to CI of 0, 0.5, or 2 Gy directed to the hypothalamus to explore the effects of low-to-moderate doses of CI on MetS risks. Despite targeting the hypothalamus as a major metabolic control center, we did not detect hypothalamic astrocyte or microglia activation at 2 or 7 days, or at 3 months post-CI. Indirect calorimetry at 2 months post-CI showed no metabolic alterations between groups, yet female mice subjected to CI were unresponsive to leptin compared with sham. Follow-up monitoring over 2 years revealed accelerated weight gain in the 2-Gy female group and glucose intolerance in both sexes following CI. Insulin sensitivity, plasma insulin, and triglycerides remained unaltered, but both male and female 2-Gy groups showed elevated VLDL and lowered HDL cholesterol levels and aberrant hypothalamic mRNA levels of genes involved in synaptic and neuronal function, neuroinflammation, and endoplasmic reticulum stress. Mortality remained unaffected by all doses of CI. These data strongly suggest a significant risk for developing MetS following low-to-moderate doses of CI, and they support tailored clinical risk assessment and monitoring strategies for patients undergoing CI, especially when the hypothalamus is included. ARTICLE HIGHLIGHTS: High-dose cranial irradiation (CI) during early developmental stages has been linked to metabolic abnormalities in later life, but causal evidence at low-to-moderate doses has been elusive. Monitoring mice for 2 years post-2-Gy CI to the hypothalamus, we found increased risks of leptin resistance, dyslipidemia, glucose intolerance, and weight gain, identifying the hypothalamus as the likely responsible region. Our findings suggest that low-to-moderate doses of CI may be a risk factor for developing metabolic syndrome. Future clinical risk assessment and monitoring strategies are needed for patients undergoing CI of hypothalamic centers governing glucose and energy metabolism.

Impact Factor

Scopus SNIP

Altmetric

7.500

0.000