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    Home > Biochemistry News > Microbiology News > "Nature" Sub-Journal: Intestinal bacteria has a secret recipe for long fat!

    "Nature" Sub-Journal: Intestinal bacteria has a secret recipe for long fat!

    • Last Update: 2022-01-11
    • Source: Internet
    • Author: User
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    The mechanism is unknown, intestinal flora?
    In recent years, researchers have discovered the association between gut microbes and many diseases, such as metabolic diseases, neurodegenerative diseases, and cancer.
    However, the findings of many studies have remained relevant and did not reveal the specific mechanisms.
    Uncertainty can easily lead to suspicion


     Therefore, many researchers have worked hard to clarify the relationship between disease and gut microbes from the mechanism

     In today’s "Nature Metabolism" magazine, researchers from Emory University School of Medicine in the United States published a new study [1], they found that a metabolite of intestinal microbes δ-valerobetaine can regulate mitochondrial fatty acids Oxidation increases lipid storage in adipose tissue and liver, leading to obesity and liver steatosis

     Obesity is probably the most frequently mentioned disease related to intestinal microbes, but the mechanism is still not clear enough

    Intestinal microbial metabolites often play the role of "signal molecules", and studies have shown that in the metabolic process, there is an interaction between microorganisms and host mitochondria, and specific signaling molecules are responsible for the communication between them [2,3 ]

     If obesity is regarded as the result of the imbalance of the microbe-host mitochondrial interaction that affects energy metabolism, then finding the key signaling molecule in this interaction may be the key to repairing the imbalance

     Therefore, researchers must first determine a gut microbial metabolite that may affect mitochondrial function

    They divided some 3-week-old sterile mice into two groups.
    For the next 3 weeks, one group continued to be sterile, and the other group ate and slept with ordinary mice, sharing their gut microbes.
    The researchers then analyzed the liver and liver mitochondrial metabolomes of the two groups of mice


     The results show that the most distinguishable metabolite is δ-valerobetaine (δ-VB), which is present in the liver and other tissues, portal vein and peripheral circulation, and cecal contents of mixed sterile mice.
    It is not present in mice that are kept sterile, nor is it in their daily diet


     δ-VB looks very strange at first glance, but it also has a precursor molecule whose identity is trimethylamine N-oxide (TMAO).
    You should be familiar with TMAO, right?
    Researchers’ experiments have shown that many kinds of gut microbes can metabolize to produce δ-VB.
    If ordinary mice are treated with antibiotics for 5 days, δ-VB can be reduced by about 25%


    The level of δ-VB produced by different intestinal microbes cultured in vitro.
    What effect will δ-VB have on metabolism?
    Using liver cell culture experiments, the researchers found that delta-VB reduces mitochondrial respiration by reducing carnitine-mediated oxidation of mitochondrial fatty acids, and the reduction of fatty acid oxidation leads to an increase in lipid accumulation


    In mice injected with delta-VB for 3 days, they observed an increase in liver triglyceride levels and an increase in lipid deposition, as well as a decrease in carnitine levels

    In other words, δ-VB affects fatty acid metabolism by disrupting the carnitine shuttle system

     Next, the researchers hope to get further corroboration in in vivo experiments

    They fed a batch of sterile mice and normal mice with a high-fat diet for more than 6 weeks, and the other group added δ-VB on this basis.
    Compared with a high-fat diet alone, a high-fat diet + δ-VB Let the mice gain more fat, whether it is visceral or subcutaneous, even sterile mice have not escaped this fate


    At the same time, liver steatosis of mice in the high-fat diet +δ-VB group was also significantly more serious

     But the good news is that if you switch from a high-fat diet to a regular diet, the effect of delta-VB becomes less obvious

     Not only mice, the researchers also conducted some studies among 15 participants in a fecal bacterial transplant (FMT) clinical trial

    Participants were randomly divided into two groups, one group only used polyethylene glycol enema as the observation group, and the other group received FMT after enema

    During the follow-up, 11 of the 15 participants had a significant increase in δ-VB, which was consistent with the initial results of the sterile mouse experiment

     The researchers also compared the delta-VB levels of 130 volunteers with a BMI>30 and 84 volunteers with a BMI<30 in the same cohort, and found that the average delta-VB level of volunteers with a BMI>30 was about 40 higher than those with a BMI<30.


    In a previously published adult cohort database (179 people), they found that plasma δ-VB and visceral fat are positively correlated (β=3.
    1×104, P=0.
    0006), and this relationship is independent Based on age, race and gender


     Plasma δ-VB and visceral fat are positively correlated.
    Similarly, another cohort data analysis of 74 patients with non-alcoholic fatty liver disease also showed that plasma δ-VB is related to liver steatosis, compared with mild steatosis and severe The plasma circulating delta-VB level in patients with steatosis is 40% higher (P=0.


     From these results, we can see that δ-VB, a metabolite of intestinal microbes, has a negative impact on metabolism.
    By regulating the oxidation of mitochondrial fatty acids, it increases lipid storage in adipose tissue and liver, leading to obesity and liver steatosis, especially It is based on the eating habit of high-fat diet


     Based on this discovery, if it can be further determined in the future that targeting delta-VB can prevent or treat obesity and related cardiometabolic diseases, then we will have a new weapon against metabolic diseases

     References: [1] https:// Bajpai P, Darra A, Agrawal A.
    Microbe-mitochondrion crosstalk and health: An emerging paradigm[J] .
    Mitochondrion, 2018, 39: 20-25.
    [3] Donohoe DR, Garge N, Zhang X, et al.
    The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon[J].
    Cell metabolism, 2011, 13( 5): 517-526.

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