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Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
Fatty acid overproduction by gut commensal microbiota exacerbates obesity
Tadashi Takeuchi1, Keishi Kameyama2, Eiji Miyauchi3
1Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
Abstract:
Although recent studies have highlighted the impact of gut microbes on the progression of obesity and its comorbidities, it is not fully understood how these microbes promote these disorders, especially in terms of the role of microbial metabolites. Here, we report that Fusimonas intestini, a commensal species of the family Lachnospiraceae, is highly colonized in both humans and mice with obesity and hyperglycemia, produces long-chain fatty acids such as elaidate, and consequently facilitates diet-induced obesity. High fat intake altered the expression of microbial genes involved in lipid production, such as the fatty acid metabolism regulator fadR. Monocolonization with a FadR-overexpressing Escherichia coli exacerbated the metabolic phenotypes, suggesting that the change in bacterial lipid metabolism is causally involved in disease progression. Mechanistically, the microbe-derived fatty acids impaired intestinal epithelial integrity to promote metabolic endotoxemia. Our study thus provides a mechanistic linkage between gut commensals and obesity through the overproduction of microbe-derived lipids.
Insights
Gut bacteria like Fusimonas intestini promote obesity by producing fatty acids that damage the gut barrier. This leads to metabolic endotoxemia and facilitates diet-induced obesity in humans and mice.
Area of Science:
- Microbiology
- Metabolic Diseases
- Gut Microbiome Research
Background:
- Gut microbes influence obesity and related conditions.
- The precise mechanisms, particularly involving microbial metabolites, remain unclear.
Purpose of the Study:
- To investigate the role of specific gut microbes and their metabolites in obesity.
- To elucidate the mechanistic link between gut commensals and diet-induced obesity.
Main Methods:
- Analysis of Fusimonas intestini colonization in obese humans and mice.
- Investigating microbial gene expression related to lipid production (e.g., fadR).
- Monocolonization experiments with engineered E. coli to assess lipid metabolism impact.
Main Results:
- Fusimonas intestini is abundant in obese and hyperglycemic individuals.
- This microbe produces long-chain fatty acids, including elaidate, promoting obesity.
- Altered microbial lipid metabolism, specifically FadR regulation, exacerbates metabolic phenotypes.
- Microbe-derived fatty acids compromise intestinal barrier integrity, leading to metabolic endotoxemia.
Conclusions:
- Gut commensals can drive obesity through the overproduction of specific lipids.
- Fusimonas intestini and its lipid metabolites represent a novel mechanistic link to obesity.
- Targeting microbial lipid metabolism may offer therapeutic strategies for obesity and related metabolic disorders.
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