The Role of The Role of  CeM-CRH^{PVH} Projection in Mediating Catecholamine Resistance and Lipogenesis in Hepatocytes Projection in Mediating Catecholamine Resistance and Lipogenesis in Hepatocytes

Mia Nurkanti; Sindi Arum Maria

Authors

Mia Nurkanti Universitas Pasundan Bandung, Indonesia https://orcid.org/0000-0002-1151-9428
Sindi Arum Maria Pusat Penelitian Perkebunan Gula Indonesia https://orcid.org/0009-0002-2918-2605

Keywords:

Chronic stress, $CeM-CRH^{PVH}$ projection, Catecholamine resistance, $\beta3$-adrenergic receptor, Lipogenesis, Hepatocytes

Abstract

Chronic stress is increasingly recognized as a significant driver of metabolic disorders, yet the precise neural-to-peripheral pathways remain poorly understood. This study aims to investigate the role of the $CeM-CRH^{PVH}$ (central nucleus of the amygdala to paraventricular nucleus of the hypothalamus) neural projection in mediating hepatic lipid metabolism. Using a combination of optogenetic stimulation, retrograde tracing, and biochemical assays in murine models, we examined the systemic impact of chronic stress on the brain-liver axis. The results demonstrate that hyperactivation of $CeM-CRH^{PVH}$ neurons leads to sympathetic nerve degeneration and subsequent catecholamine resistance in the liver. This disruption causes a significant downregulation of $\beta3$-adrenergic receptors ($\beta3$-AR) in hepatocytes, which triggers a metabolic shift characterized by increased lipogenesis and suppressed lipolysis. Consequently, these changes culminate in accelerated lipid deposition and the development of hepatic steatosis. In conclusion, this research identifies the $CeM-CRH^{PVH}$ circuit as a critical mediator of stress-induced fatty liver, suggesting that targeting this specific neural projection or restoring $\beta3$-AR signaling could offer novel therapeutic strategies for metabolic diseases. These findings provide a robust framework for integrating neuro-metabolic research into advanced biotechnological and medical curricula.

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References

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