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Gut-derived Metabolites link Intestine, Liver, and Heart in Metabolic Regulation
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A new study reveals how compounds originating in the gut microbiome travel to the liver and heart, influencing metabolic pathways and insulin sensitivity, possibly opening avenues for treating obesity and type 2 diabetes.
What Was Found
A research project supported by FAPESP and carried out at Harvard University in the United States has identified a set of metabolites that move from the intestine to the liver and than on to the heart, which distributes them throughout the body. These circulating compounds appear to influence how metabolic pathways function within the liver and how sensitive the body is to insulin. The findings point to potential new strategies for treating obesity and type 2 diabetes. The study was published in cell Metabolism.
The research, led by Vitor Rosetto Muñoz, a postdoctoral researcher at the Ribeirão Preto School of Physical Education and Sports at the University of São Paulo (EEFERP-USP) in brazil, focused on tracing the journey of metabolites from the gut to other organs. “The hepatic portal vein drains much of the blood from the intestine to the liver. Therefore, it’s the first place to receive products from the gut microbiome. In the liver, they can be conjugated, transformed, or eliminated, and then enter the systemic circulation,” explains Muñoz.
By comparing blood samples taken from the intestine and peripheral circulation, the researchers were able to pinpoint how these gut-derived metabolites accumulate in different locations and impact hepatic metabolism and overall metabolic health. Muñoz conducted this research during an internship at the Joslin Diabetes Center at Harvard Medical School, supported by a FAPESP scholarship, under the guidance of Carl Ronald Kahn.
The Gut Microbiome’s Role in Metabolic Health
Gut Microbiome Diversity and Metabolic Disease risk
The gut microbiome has emerged as a critical factor in the growth of metabolic disorders. Individuals with obesity,type 2 diabetes,glucose intolerance,or insulin resistance consistently exhibit distinct gut microbial compositions compared to healthy individuals. Research demonstrates a strong correlation between gut microbiome composition and metabolic health.
Though, identifying the specific bacterial species or microbial products responsible for these differences, and understanding their mechanisms of action, remains a significant challenge. This study aimed to address this gap by examining metabolites in the blood of mice with varying susceptibility to obesity and diabetes.
How the Study Was Conducted
The researchers analyzed blood samples from mice,focusing on metabolites – small molecules produced by the metabolism of bacteria. They compared metabolite profiles in blood leaving the intestine (via the hepatic portal vein) and blood circulating throughout the body.This allowed them to identify metabolites that were enriched in specific locations and assess their impact on liver function and metabolic health.
The study utilized a mouse model with varying genetic predispositions to obesity and diabetes, allowing researchers to observe how gut-derived metabolites influenced metabolic outcomes in different individuals. The team employed metabolomics, a powerful technique for identifying and quantifying a wide range of metabolites in biological samples.
Key Findings and Implications
The study identified a specific set of metabolites that were considerably enriched in the blood leaving the intestine and later found in the liver and heart. These metabolites appeared to modulate key metabolic pathways in the liver, influencing glucose metabolism and insulin sensitivity.
Specifically,the researchers found that these metabolites impacted the expression of genes involved in glucose production and lipid metabolism in the liver. This suggests that the gut microbiome can directly influence liver function and contribute to the development of metabolic disorders.
The findings suggest that manipulating the gut microbiome – thru dietary interventions, prebiotics, or probiotics – coudl potentially improve metabolic health and prevent or treat obesity and type 2 diabetes. Further research is needed to identify the specific bacterial species responsible for producing these beneficial metabolites and to develop targeted interventions.
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