How does metabolism affect the expression of microRNAs in macrophages?
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Metabolism significantly influences the expression of microRNAs in macrophages. Studies have shown that macrophages adjust their metabolic programs to regulate gene expression and inflammatory responses, with microRNAs playing a crucial role in this process . In conditions like obesity, oxidative stress triggers dysregulation of signaling pathways, altering the expression of various microRNAs in organs involved in glucose and lipid metabolism regulation . Specifically, miR-210 induction in activated macrophages supports a switch towards a proinflammatory state by modulating metabolism, favoring glycolysis over mitochondrial respiration, partly through downregulating the ISCU enzyme . Additionally, obesity influences adipose tissue miRNAs in a cell-specific manner, with macrophage miR-155 potentially impacting neighboring adipocytes, showcasing the intricate relationship between metabolism, microRNAs, and macrophages .
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| Papers (5) | Insight |
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| Metabolism influences miR-210 expression in macrophages by promoting a shift towards glycolysis over mitochondria respiration, modulated by downregulating ISCU, impacting inflammatory responses during pathogen interactions. | |
| Metabolism-related factors like hyperglycemia, insulin resistance, and obesity alter microRNA expression in organs involved in glucose and lipid metabolism, impacting oxidative stress in metabolic syndrome. | |
21 Citations | Metabolism influences macrophage microRNA expression, with miR-155 and miR-210 increasing in obesity. Macrophage-derived miR-155 targets PPAR-γ, impacting adipocyte metabolism in a cell-specific manner. |
16 Citations | Metabolic pathways impact microRNA expression in macrophages, regulating gene expression and inflammatory responses, as highlighted in the interplay between miRNAs and metabolism during macrophage inflammatory reactions. |
23 Citations | Metabolism influences microRNA expression in macrophages, impacting their polarization and function, particularly in obesity-associated diseases like insulin resistance through regulation of macrophage activation states. |
Related Questions
What is the role of lncRNA for metabolism of leishmania infected macrophage?10 answersLong noncoding RNAs (lncRNAs) play a significant role in the metabolic reprogramming of macrophages infected by Leishmania, impacting both the host's immune response and the parasite's survival strategy. In Leishmania-infected macrophages, more than 24% of the total annotated transcripts correspond to lncRNAs, indicating a substantial alteration in the macrophage transcriptome that includes both lncRNAs and protein-coding RNAs. These changes are similar across infections by different Leishmania species, suggesting a common mechanism of macrophage manipulation by the parasite, although species-specific alterations do occur.
The metabolic pathways of macrophages, including carbohydrate and lipid metabolisms, are significantly altered following Leishmania infection, with a shift towards anaerobic glycolysis and disturbances in cholesterol and triglyceride homeostasis. This metabolic shift is further complicated by the parasite's manipulation of host cell mitochondrial energy metabolism, pushing macrophages from glycolytic metabolism to oxidative phosphorylation, a process requiring the activation of SIRT1 and AMPK, which are essential for parasite growth.
LncRNA HOTAIR, for instance, has been shown to regulate glucose metabolism in macrophages during inflammation, indicating a potential role in metabolic reprogramming during Leishmania infection. Metabolic profiling of infected macrophages reveals significant changes in metabolites, including increased levels of potential parasite end products like succinate, acetate, and alanine, highlighting the metabolic interplay between host and parasite.
Leishmania infection induces a mixed, immunometabolomic polarization profile in macrophages, characterized by both M1 and M2 markers and a unique bioenergetic signature, suggesting that the parasite modulates host cell metabolism to balance immune responses conducive to its survival. Furthermore, the involvement of lncRNAs in the immunopathology of visceral leishmaniasis, through regulation of protein-coding genes involved in immune responses, underscores their role in the complex regulatory networks governing host-parasite interactions.
Leishmania's ability to proliferate within macrophages is linked to programmed changes in carbon metabolism and growth rate, highlighting the importance of metabolic processes as key virulence determinants. The modulation of host cell functions by miRNAs, such as MIR30A-3p, which regulates autophagy by targeting BECN1, further illustrates the intricate regulatory mechanisms at play, including those mediated by lncRNAs. Finally, the nutritional requirements of Leishmania, which must be scavenged from the host cell, and the impact of host cell activation on nutrient availability to the parasite, emphasize the critical role of metabolic processes in disease outcome.
In summary, lncRNAs contribute to the metabolic reprogramming of Leishmania-infected macrophages by regulating key metabolic pathways and immune responses, thereby facilitating parasite survival and proliferation within the host.
What is the impact on macrophage function due to metabolic stress?5 answersMetabolic stress significantly impacts macrophage function by inducing alterations in their immunometabolic profile. This stress can lead to reduced oxidative phosphorylation, increased glycolysis, and elevated production of reactive oxygen species. Macrophages, crucial in immune responses, exhibit plasticity in response to metabolic stress, with specific metabolic signatures dictating their functions. Chronic inflammation resulting from metabolic stress, often due to lipid overload, can lead to dysregulated immune responses and contribute to diseases like obesity and atherosclerosis. In adipose tissue, metabolic stress alters the composition of adipose tissue macrophages, impacting their endocytic capacity and gene expression profiles. Overall, metabolic stress plays a pivotal role in modulating macrophage function, highlighting the intricate link between metabolism and immune responses.
What is the role of Post-transcriptional regulation for metabolism of leishmania infected macrophage?10 answersPost-transcriptional regulation plays a pivotal role in the metabolism of macrophages infected by Leishmania, influencing various aspects of the host cell's response and the parasite's survival strategy. In Leishmania-infected macrophages, post-transcriptional mechanisms are crucial for regulating the immune and metabolic responses, including alterations in the host cell's transcription factors that orchestrate leishmanicidal and inflammatory reactions against the parasite. This regulation extends to the manipulation of macrophage miRNA profiles by the parasite, affecting genes involved in the inflammatory immune response, which is mediated through microRNA-mediated post-transcriptional regulation.
Leishmania parasites have developed sophisticated strategies to manipulate host macrophage miRNA expression, thereby influencing macrophage physiology to promote parasite survival. This includes the exploitation of transcription factor c-Myc by Leishmania to regulate the abundance of macrophage miRNAs. Moreover, the interaction between Leishmania and macrophages leads to significant metabolic shifts within the host cell, such as a transition to anaerobic glycolysis and alterations in lipid metabolism, which are indicative of post-transcriptional regulation effects.
The impact of post-transcriptional regulation on macrophage metabolism is further highlighted by the differential expression of genes associated with metabolism in dendritic cells infected by Leishmania, suggesting a broader influence on the host's immune cells. Additionally, genome instability in Leishmania donovani, a factor in the parasite's adaptation and survival, results in gene dosage-dependent and independent changes affecting post-transcriptional regulation, which in turn influences the host cell's metabolic pathways.
Furthermore, the selective reprogramming of the host cell's translational landscape by L. donovani, including the modulation of mRNA translation affecting key metabolic processes, underscores the significance of post-transcriptional and translational regulation in shaping the metabolic environment of Leishmania-infected macrophages. This complex regulatory network, involving both direct and indirect gene dosage effects, highlights the intricate interplay between Leishmania and its host cell, where post-transcriptional regulation serves as a critical mechanism for both parasite survival and host cell metabolic adaptation. Lastly, the differential gene expression observed in macrophages infected with L. (V.) braziliensis, particularly in pathways related to sterol and cholesterol biosynthesis, further emphasizes the role of post-transcriptional regulation in modulating the metabolic response of the host cell to Leishmania infection.
How does the inflammatory environment affect the metabolism of M2 macrophages?5 answersThe inflammatory environment significantly impacts the metabolism of M2 macrophages. In response to inflammation, macrophages exhibit changes in their metabolic status, including alterations in glycolysis, mitochondrial respiration, and nutrient uptake. This metabolic reprogramming is crucial for regulating inflammation and maintaining homeostasis, especially in diseases like rheumatoid arthritis. Furthermore, the interplay between environmental signals and pathogenic cues determines macrophage metabolism, shaping the type and intensity of the immune response. In the context of cancer, such as acute myeloid leukemia, M2-polarized macrophages exhibit enhanced fatty acid oxidation and NAD+ generation, supporting tumor growth by reducing phagocytic activity and promoting leukemic blast cell survival. Modulating macrophage metabolism emerges as a potential therapeutic strategy for inflammatory diseases and cancer.
Are there any clinical studies exploring the potential of metabolism-related miRNAs in cancer?5 answersMetabolism-related miRNAs have been explored in clinical studies for their potential in cancer. These miRNAs have been investigated as diagnostic, prognostic, and predictive tools in various types of cancer, including prostate cancer, non-small cell lung cancer (NSCLC), and other human and canine cancers. They have shown promise in regulating gene expression, influencing cancer initiation and progression, and predicting treatment response and resistance. Studies have identified specific miRNAs associated with lipid metabolism in prostate cancer, which could serve as diagnostic markers and therapeutic targets. In prostate cancer, miRNAs have been studied in relation to androgen receptor signaling, epithelial-mesenchymal transition, and cancer stem cell regulation. In NSCLC, miRNAs have been implicated in cell proliferation, migration, invasion, metastasis, and resistance to anti-cancer drugs. These findings highlight the potential of metabolism-related miRNAs as valuable tools in cancer research and personalized treatment strategies.
How dose metabolism affect gene expression?3 answersMetabolism affects gene expression by modifying the epigenome, which can regulate stem cell pluripotency, differentiation, and somatic cell reprogramming. Metabolic pathways provide the precursor molecules necessary for gene expression and ATP, the primary fuel driving gene expression. Changes in substrate availability can alter metabolic gene expression to modify the utilization of nutrients appropriately. Enzymes involved in adding and removing histone tail modifications, which regulate gene expression, require cofactors that are products of intermediary metabolism pathways. Under- and over-nutrition can induce epigenetic changes that influence chromatin structure and define a metabolic program. Metabolic gene expression can be dysregulated in disease states, such as diabetes, due to persistent changes in chromatin structure. Overall, metabolism plays a crucial role in regulating gene expression through its influence on the epigenome and the availability of metabolic products as cofactors for enzymes involved in modifying chromatin structure.