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Barkan-Michaeli, R.

Publications and source records attributed to Barkan-Michaeli, R..

2 recordsLinked to original sources

Insular cortex predictions regulate glucose homeostasis

Brain-body interactions are essential for physical and emotional homeostasis. The brain uses information from the external world to predict upcoming bodily changes. This process involves interoceptive predictions, which are thought to play a central role in brain-body interactions. Yet there is little direct experimental evidence causally linking interoceptive predictions to regulation of bodily physiology. Here we address this by focusing on insular cortex and glucose homeostasis. We find that just before the onset of a meal, insular cortex exhibits a transient burst of activity, reflecting a prediction of the future metabolic state. This transient predictive burst of activity is essential for anticipatory insulin release, subsequent post-meal insulin release, post-meal glucose and lipid homeostasis, and post-meal metabolism signaling in the liver. Our results highlight that insular cortex predictive computations are essential for anticipatory physiological control and for subsequently maintaining metabolic homeostasis.

neuroscience↗

Chemokine Signaling Shapes Hepatic Lipid Homeostasis through the CXCL12/CXCR4/CXCR7 Axis

The CXCL12/CXCR4/CXCR7 signaling axis, long recognized for its roles in cancer, fibrosis, and tissue repair, is emerging as a broader regulator of tissue homeostasis. Here, we uncover a previously unappreciated function of this pathway in regulating hepatic metabolism. We show that Cxcl12, Cxcr4, and Ackr3 (encoding CXCR7) are dynamically regulated during the fasting-refeeding transition and become dysregulated under conditions of diet-induced insulin resistance. Hepatocyte-specific depletion of Cxcl12 or overexpression of Ackr3 each led to hepatic triglyceride accumulation, whereas hepatocyte Cxcr4 overexpression did not reproduce this phenotype, supporting a nonredundant role for CXCR7 in hepatocytes. Hepatic SDF-1 measurements across the three in vivo models further supported coordinated regulation of ligand availability within the axis, including a marked reduction in the Ackr3 overexpression model, consistent with enhanced ligand scavenging. In primary hepatocytes, Ackr3 overexpression promoted lipid accumulation and was associated with altered AKT-linked signaling, particularly under lipid-rich conditions. Analysis of human liver transcriptomic datasets revealed reduced CXCL12 and elevated CXCR4 and ACKR3 expression in NAFLD and NASH, supporting the translational relevance of this pathway. Together, our results identify the CXCL12/CXCR4/CXCR7 axis as an integral regulator of hepatic lipid balance and highlight CXCR7 as a potential therapeutic target for metabolic liver disease.

physiology↗