Longitudinal Profiling Reveals Divergent Kidney and Brain Immune Responses during Metabolic Syndrome.

Authors

Laura Van der Taelen, Sara M P Lambrichts, Lieve Temmerman, Romaysa El Ajjouri, Marion J Gijbels, Nicole Bitsch, Jean Scheijen, Marjo van de Waarenburg, Martina Kutmon, Thomas Unger, Julie Staals, Casper G Schalkwijk, Ana M Briones, Robert J van Oostenbrugge, Sébastien Foulquier

Published in

Aging and disease. Aug 11, 2026. Epub Aug 11, 2026.

Abstract

Chronic kidney disease (CKD) and cerebral small vessel disease (cSVD) share major cardiometabolic risk factors, including hypertension, diabetes, and obesity. The immune system may play a key role in kidney-brain interactions and disease development. However, whether circulating inflammatory mediators reflect similar immune responses in the kidney and brain remains unclear. We therefore characterized circulating, renal and cortical cerebral responses in a rat model of metabolic syndrome. Lean and Obese ZSF1 rats were studied at 8-9, 22-23, and 34-35 weeks of age. Systemic inflammation was assessed using multiplex plasma cytokine/chemokine analysis and flow cytometry of circulating immune cells. Kidney injury was evaluated by histopathology and expression of injury markers. Renal and cerebral blood flow were measured by Laser Speckle Contrast Imaging. Renal macrophage accumulation and cortical cerebral immune cell readouts were assessed by immunohistochemistry. Progression of metabolic syndrome in Obese ZSF1 rats was associated with elevated circulating inflammatory mediators, including IP-10, MCP-1, and RANTES, together with increased classical monocytes from 8-9 weeks and non-classical monocytes from 22-23 weeks onward. Kidney pathology was further characterized by progressive macrophage accumulation and reduced renal blood flow. In contrast, cortical cerebral analyses showed no evidence of macrophage infiltration, while CD68 positivity was reduced in Iba1+ microglia in Obese rats at 34-35 weeks. Despite marked systemic inflammation and renal immune activation, the cerebral cortex displayed a distinct immune response with no macrophage infiltration and altered microglial activity. Rather than indicating a uniform inflammatory response across organs, these descriptive findings provide insight into kidney-brain immune divergence during metabolic syndrome.

PMID:
42691223
Bibliographic data and abstract were imported from PubMed on 04 Sep 2026.

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