Core Mechanisms and Research Advances in Gut Microbiota Regulation of Energy Metabolism Driving Obesity
DOI:
https://doi.org/10.54097/8c0mm687Keywords:
Gut Microbiota, Obesity, Energy Metabolism, Short-chain Fatty Acids, Bile Acids, Lipopolysaccharides, FXR, TGR5Abstract
The global obesity problem is still increasing, influenced not only by dietary patterns but also by the important part played by dysbiosis in the gut microflora. The gut bacteria control the body's energy metabolism through various pathways, interfering with the relationship between energy intake and expenditure to cause obesity. This study investigates the main mechanisms by which the gut microflora affect the energy metabolism to result in obesity, particularly involving the influence of short-chain fatty acids (such as acetic, propionic and butyric acids) on energy intake, lipid synthesis and insulin signalling; the promotion of fat absorption and disruption of energy expenditure through the FXR and TGR5 receptors by bile acids; the induction of chronic inflammation and insulin resistance by lipopolysaccharides; and the regulation of factors like leptin and adiponectin by the microflora to change the appetite and energy homeostasis. It also gathers the classic experimental data indicating the association between the microflora and obesity. Current research offers theoretical basis for the prevention and treatment of obesity by means of gut microflora intervention. However, it is necessary to carry out further investigations into the effectiveness of the microflora metabolites and personalized regulation of human microflora. Precise interventions focusing on the gut microflora will become an important direction in the management of obesity.
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[1] Bäckhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., Semenkovich, C. F., & Gordon, J. I. (2004). The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences of the United States of America, 101(44), 15718–15723. https://doi.org/10. 1073/ pnas.0407076101.
[2] Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122), 1009–1010. https://doi.org/ 10.1038/ nature 05414.
[3] Ley, R. E., Turnbaugh, P. J., Klein, S., & Gordon, J. I. (2006). Microbial ecology: human gut microbes associated with obesity. Nature, 444(7122), 1022–1023. https://doi.org/10. 1038/ nature05414.
[4] Koh, A., De Vadder, F., Kovatcheva-Datchary, P., & Bäckhed, F. (2016). From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell, 165(6), 1332–1345. https://doi.org/10.1016/j.cell.2016.05.041.
[5] Parada Venegas, D., De la Fuente, M. K., Landskron, G., González, M. J., Quintero, P. A., Mondragón, M., et al. (2019). Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Frontiers in Immunology, 10, 277. https://doi.org/ 10. 3389/ fimmu.2019.00277.
[6] Perry, R. J., Peng, L., Barry, N. A., Cline, G. W., Zhang, D., Cardone, R. L., et al. (2016). Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature, 534(7606), 213–217. https://doi.org/10.1038/nature18309.
[7] Zhao, S., Yu, H., Zhang, Y., Zhang, C., Zhu, L., Li, N., et al. (2020). Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate. Nature, 579(7800), 586–591. https: // doi.org/10.1038/s41586-020-2110-7.
[8] Linares, A., Tirosh, A., Calay, E. S., Levie, S., Nudelman, A., Kuperman, Y., et al. (2019). The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans. Science Translational Medicine, 11(488), eaav0120. https://doi.org/ 10. 1126/ scitranslmed. aav0120.
[9] Canfora, E. E., van der Beek, C. M., Troost, F. J., & Bakker, B. M. (2015). Increased intestinal nutrient absorption in obesity: Role of short-chain fatty acids. Gut, 64(6), 898–907. https: //doi. org/10.1136/gutjnl-2014-308902.
[10] Peng, L., Li, Y. R., Chen, L., Zeng, H., Yang, D. Q., Zhou, X. Y., et al. (2009). Butyrate enhances adipocyte differentiation and insulin sensitivity via peroxisome proliferator-activated receptor γ. Diabetes, 58(1), 150–159. https://doi.org/ 10. 2337/ db08-1605.
[11] Chiang, J. Y. (2009). Bile acids: Regulation of synthesis. Journal of Lipid Research, 50(10), 1955–1966. https:// doi. org/ 10. 1194/jlr.R900011-JLR200.
[12] Sahuri, A., Tawadros, S., Hammad, S., Prawitt, J., Cohrs, C. M., Klingenspor, M., et al. (2021). Intestinal TGR5 drives lipid absorption and obesity via CD36/FATP4-dependent fatty acid uptake. Molecular Metabolism, 48, 101196. https://doi. org/10. 1016/ j.molmet.2021.101196.
[13] Ferrell, J. M. (2020). Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy. American Journal of Physiology-Gastrointestinal and Liver Physiology, 318(6), G554–G573. https://doi.org/10.1152/ajpgi.00223.2019.
[14] Kumar, P., Schroder, E. A., Rajaram, M. V. S., Harris, E. N., & Ganesan, L. P. (2024). The battle of LPS clearance in host defense vs. inflammatory signaling. International Journal of Molecular Sciences, 13(18), 1590. https://doi.org/10.3390/ ijms13181590.
[15] Sul, O. J., & Ra, S. W. (2021). Quercetin prevents LPS-induced oxidative stress and inflammation by modulating NOX2/ROS/NF-κB in lung epithelial cells. International Journal of Molecular Sciences, 26(22), 6949. https://doi.org/ 10. 3390/ ijms26226949.
[16] Obradovic, M., Sudar-Milovanovic, E., Soskic, S., Essack, M., Arya, S., Stewart, A. J., Gojobori, T., & Risenovic, E. (2021). Leptin and obesity: Role and clinical implication. International Journal of Molecular Sciences, 12(10), 5858. https://doi.org/ 10. 3390/ijms12105858.
[17] Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastard, J. P., et al. (2007). Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 56(7), 1761–1772. https:// doi.org/10.2337/db06-1497.
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