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The de novo synthesis of GABA and its gene regulatory function are indispensable for HCC metastasis

ABSTRACT: To investigate the mechanism of GABA in the regulation of liver cancer metastasis, we treated Huh7 cell lines with or without GABA. We then performed gene expression profiling analysis using data obtained from RNA-seq.

ORGANISM(S): Homo sapiens

PROVIDER: GSE277311 | GEO | 2024/11/23

REPOSITORIES: GEO

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The de novo synthesis of GABA and its gene regulatory function are indispensable for HCC metastasis

Project description:The de novo synthesis of GABA and its gene regulatory function are indispensable for HCC metastasis

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Project description:Neurotransmitters have been well-documented to determine immune cell fates; however, whether and how γ-amino butyric acid (GABA) shapes the function of innate immune cells is still obscure. Here, we demonstrated that GABA orchestrates macrophage maturation and inflammation. GABA treatment during macrophage maturation inhibits interleukin (IL)-1β production from inflammatory macrophages. Mechanistically, GABA enhances succinate-FAD-lysine demethylase1 (LSD1) signaling to regulate the histone demethylation of Bcl2l11 and Dusp2, lowering the formation of NLRP3-ASC-Caspase-1 complex. Meanwhile, GABA-succinate axis lowers succinylation of mitochondrial proteins to promote mitochondrial oxidative phosphorylation (OXPHOS). We also found that GABA alleviates the LPS-induced sepsis as well as high-fat diet-induced obesity in mice. Our study proves that GABA is potential in lessening the pro-inflammatory macrophage responses associating with metabolic reprogramming and protein succinylation, thus providing a strategy for treating macrophage-related inflammatory diseases.

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A Critical Role of Hepatic GABA in The Metabolic Dysfunction and Hyperphagia of Obesity

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De novo NAD<sup>+</sup> synthesis enhances mitochondrial function and improves health.

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