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    Home > Active Ingredient News > Endocrine System > Sub-Journal of "Cell": Chinese medicine extract opens up a new direction for fat burning!

    Sub-Journal of "Cell": Chinese medicine extract opens up a new direction for fat burning!

    • Last Update: 2021-03-21
    • Source: Internet
    • Author: User
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    In 2009, some studies found that there is activatable brown fat in adults.

    Brown fat is a "good thing", it contributes to energy consumption and the metabolism of blood sugar and free fatty acids.
    It was once regarded as a new hope for the treatment of obesity and related metabolic diseases.

    However, the amount of brown fat is too small in adults, and it is more difficult to achieve the goal of weight loss by "burning fat".

     Is there any other way to burn fat? Recently, researchers from the Sixth People's Hospital Affiliated to Shanghai Jiaotong University and China Pharmaceutical University published new research results in the journal Cell Metabolism [1].

     They found that Hypericin, an extract of Hypericum perforatum, can activate AMPK signal through the target of dihydrolipidamide S-acetyltransferase (Dlat), stimulate adipose tissue to produce heat, and successfully prevent the occurrence of obesity in mice.
    It can also improve the metabolic dysfunction of obese mice.

    They also found that DLAT mutations are significantly related to human obesity.

    This research opens up a new direction for the treatment of obesity.

    Picture from pexels.
    com Although activating brown fat to lose weight and improve metabolism is currently not feasible, the mechanism that it promotes thermogenesis of fat is instructive for researchers.

     Exposure to the cold environment is a known factor that stimulates the conversion of white fat to brown fat and produces heat, but the mechanism behind this is not clear enough, and the use of this mechanism to develop drugs is limited.

    Therefore, the researchers used a tool called "CMap" (http://clue.
    io/cmap).
    What CMap provides is a systematic method that can map the gene expression profile associated with each small molecule compound Correlation, to evaluate the match between the induced transcriptional changes and the physiological state changes.Prior to this, a research team has used CMap to successfully screen out two small molecule compounds with leptin sensitivity, which have potential clinical value [2,3].

     This time, the researchers first performed RNA sequencing on the white fat and brown fat of mice exposed to the cold environment, and created a cold-induced "gene signature".
    Using it as a matching object, 21 types of commercially available products were screened through CMap.
    Among the small molecular compounds, Hypericum perforatum extract, hypericin is the most promising one.

     In vitro experiments show that hypericin increases the expression level of thermogenesis-related genes and the number of mitochondria in fat cells, and enhances cell respiration.

     In the mouse experiment, under the same food intake, the hypericin-injected mice gained significantly slower weight than the control group, the lean body mass was the same, and the total fat mass was less.

    At the same time, their white fat volume, the volume and diameter of individual fat cells are also small.

    Comparison of the weight gain of hypericin-injected mice (red) and control mice (black).
    In mice fed a high-fat diet, the experimental results are also consistent.
    After the mice are no longer injected with hypericin Within 3 weeks, the body weight remained stable, significantly lower than the control group, indicating that the effect of hypericin is not only powerful, but also long-lasting.

     Hypericin can also accelerate the speed of weight loss in mice whose diets are adjusted to cause obesity.

    High-fat diet + injection control group (black), high-fat diet after 5 weeks of diet change + injection control group (green), high-fat diet + injection of hypericin (red), high-fat diet after 5 weeks of diet change + injection The weight change of hypericin (purple) mice The respiratory exchange ratio and oxygen consumption rate of hypericin injected mice are higher than those of the control group, which means that they consume more energy and are in a cold environment at 4°C At medium time, the hypericin group mice were more resistant to cold and warm, indicating that hypericin enhanced the heat production of fat.

    Of course, the glucose homeostasis of these mice was also significantly improved.

     By studying the changes in thermogenesis-related signal pathways during hypericin treatment, the researchers found that the core of these changes lies in the activation of AMPK signaling, which promotes the expression of Ucp1 and other thermogenesis genes by increasing the level of PGC1α protein.

     Further experiments determined that the direct target of hypericin to activate AMPK is Dlat, and the main binding site is in the (I) domain.

    Although few studies have shown that Dlat plays an important role in thermogenesis of adipose tissue, the results of this experiment show that knocking out Dlat can eliminate the activation of AMPK and the increase in Ucp1 expression caused by hypericin.

     A genome-wide association study involving 697,734 Europeans found that DLAT is a gene related to obesity susceptibility, and its single nucleotide polymorphism (rs10891314) is closely related to obesity [4], the researchers found , This site is located exactly in the (I) domain.

    In addition, the sequencing results of adipose tissue samples collected by the researchers of non-obese healthy volunteers and obese volunteers also showed that the expression of DLAT in the adipose tissue of obese volunteers was significantly lower.

     In summary, this study has discovered a small molecule-hypericin that can improve obesity and metabolic function through the thermogenesis mechanism of adipose tissue, and revealed that its mechanism of action is the Dlat-AMPK pathway, which is the same as the previous findings.
    Different β3-adrenergic receptor pathways that can stimulate adipose tissue to produce heat are different.
    At present, most β3-adrenergic receptor agonists generally have cardiovascular side effects, and their application in the treatment of obesity is limited.
    The discovery may bring us new possibilities.  References: [1] Chen S, Liu X, Peng C, et al.
    The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity[J].
    Cell Metabolism, 2021, 33(3): 565-580.
    e7.
    [2] Liu J, Ibi D, Taniguchi K, et al.
    Inflammation improves glucose homeostasis through IKKβ-XBP1s interaction[J].
    Cell, 2016, 167(4): 1052-1066.
    e18.
    [ 3] Lee J, Liu J, Feng X, et al.
    Withaferin A is a leptin sensitizer with strong antidiabetic properties in mice[J].
    Nature medicine, 2016, 22(9): 1023-1032.
    [4] Pulit SL, Stoneman C, Morris AP, et al.
    Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry[J].
    Human molecular genetics, 2019, 28(1): 166-174.
    | Ying Yuyan
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