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Hepatic ChREBP is a Driver of Pathological Cardiac Remodeling via Non-Transcriptional Repression of Apolipoprotein M

ABSTRACT: Pathological cardiac remodeling is a major risk factor for heart failure, and that the hepatic transcription factor ChREBP typically regulates glucose and lipid metabolism by translocating to the nucleus to exert transcriptional regulatory functions. Furthermore, the liver-secreted protein ApoM exerts cardiovascular protective effects, and inter-organ crosstalk plays a role in systemic homeostasis. This study now reveals that in response to cardiac stress, ChREBP is specifically upregulated in the hepatocyte cytoplasm-not the nucleus-where it interacts with the ER protein SURF4 to inhibit ApoM secretion. We identify the restoration of this liver-heart axis via the ChREBP-SURF4-ApoM pathway and subsequent activation of cardiac S1P/S1PR1 signaling as a novel mechanistic basis for ameliorating cardiac remodeling, offering a promising therapeutic strategy for heart failure.

ORGANISM(S): Mus musculus

PROVIDER: GSE337074 | GEO | 2026/08/17

REPOSITORIES: GEO

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Hepatic ChREBP is a Driver of Pathological Cardiac Remodeling via Non-Transcriptional Repression of Apolipoprotein M

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