Tracking CSF inflammatory signatures in an ovine model of leptin resistance
5 affiliations
- 1Laboratory of Recombinant Proteins Production, University of Agriculture in Krakow
- 2Department of Basic Sciences, University of Agriculture in Krakow
- 3Department of Animal Biotechnology, University of Agriculture in Krakow
- 4Department of Animal Physiology and Endocrinology, University of Agriculture in Krakow
- 5Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences
Abstract
Leptin resistance is a key metabolic feature of diet-induced obesity in sheep, with implications for body condition management and reproductive efficiency. However, changes in central inflammatory mediators during its development remain poorly characterized in longitudinal settings. The present study examined dynamic changes in cerebrospinal fluid (CSF) cytokine, chemokine, and microRNA (miRNA) profiles in an ovine model of leptin resistance. Sixteen ovariectomized Polish Longwool ewes were assigned to control (CTRL, n = 5), food-restricted (LEAN, n = 5), and high-energy diet (OBESE, n = 6) groups over a 14-week period. CSF was collected weekly from the third brain ventricle and analysed for 13 cytokines and chemokines by Luminex multiplex immunoassay; five inflammation-related miRNAs were quantified by digital PCR. Obese animals exhibited elevated CSF IL-8, TNF-α, MIP-1α, and IP-10, alongside upregulation of miR-155-5p, miR-21-5p, miR-125b-5p, and miR-223-3p. TNF-α correlated positively with miR-155-5p (r = 0.68, p = 0.015), while IP-10 was inversely associated with miR-146a-5p (r = − 0.61, p = 0.036). Food-restricted animals displayed distinct CSF inflammatory profiles, with IL-1α and IL-6 exceeding obese levels at several time points, indicating that nutritional stress, independent of hyperleptinemia, can drive central inflammatory changes. These findings demonstrate coordinated CSF cytokine and miRNA signatures associated with diet-induced obesity and caloric restriction, supporting longitudinal CSF profiling as an approach for monitoring central neuroimmune dynamics in large-animal models.
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BibTeX
@article{oclon2026tracking,
title = {{Tracking CSF inflammatory signatures in an ovine model of leptin resistance}},
author = {Ewa Ocłoń and Igor Jasielczuk and Małgorzata Szczęsna and Joanna Zubel – Łojek and Tomasz Misztal and Dorota Anna Zieba},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-63046-5},
url = {https://doi.org/10.1038/s41598-026-63046-5},
note = {CC BY},
}
RIS
TY - JOUR
TI - Tracking CSF inflammatory signatures in an ovine model of leptin resistance
AU - Ewa Ocłoń
AU - Igor Jasielczuk
AU - Małgorzata Szczęsna
AU - Joanna Zubel – Łojek
AU - Tomasz Misztal
AU - Dorota Anna Zieba
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-63046-5
UR - https://doi.org/10.1038/s41598-026-63046-5
AB - Leptin resistance is a key metabolic feature of diet-induced obesity in sheep, with implications for body condition management and reproductive efficiency. However, changes in central inflammatory mediators during its development remain poorly characterized in longitudinal settings. The present study examined dynamic changes in cerebrospinal fluid (CSF) cytokine, chemokine, and microRNA (miRNA) profiles in an ovine model of leptin resistance. Sixteen ovariectomized Polish Longwool ewes were assigned to control (CTRL, n = 5), food-restricted (LEAN, n = 5), and high-energy diet (OBESE, n = 6) groups over a 14-week period. CSF was collected weekly from the third brain ventricle and analysed for 13 cytokines and chemokines by Luminex multiplex immunoassay; five inflammation-related miRNAs were quantified by digital PCR. Obese animals exhibited elevated CSF IL-8, TNF-α, MIP-1α, and IP-10, alongside upregulation of miR-155-5p, miR-21-5p, miR-125b-5p, and miR-223-3p. TNF-α correlated positively with miR-155-5p (r = 0.68, p = 0.015), while IP-10 was inversely associated with miR-146a-5p (r = − 0.61, p = 0.036). Food-restricted animals displayed distinct CSF inflammatory profiles, with IL-1α and IL-6 exceeding obese levels at several time points, indicating that nutritional stress, independent of hyperleptinemia, can drive central inflammatory changes. These findings demonstrate coordinated CSF cytokine and miRNA signatures associated with diet-induced obesity and caloric restriction, supporting longitudinal CSF profiling as an approach for monitoring central neuroimmune dynamics in large-animal models.
SN - 2045-2322
ER -