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    Home > Active Ingredient News > Endocrine System > Sub-Journal of "Nature": High-fat diet transforms mesenteric lymphatic vessels into "old and broken small"!

    Sub-Journal of "Nature": High-fat diet transforms mesenteric lymphatic vessels into "old and broken small"!

    • Last Update: 2021-11-04
    • Source: Internet
    • Author: User
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    The eleventh small holiday has passed, and the next holiday is far away, far away, hopeless
    .

    Including singular cakes, I believe that many people have arranged various "three high" meals for themselves during the small holiday.
    Anything high in sugar, high salt, and high fat is all happy~ Today, in order to increase everyone's crazy eating The guilt before eating wildly, singularity cakes have to talk about the dangers of high-fat diet
    .

     Recently, Enyuan Cao and her colleagues from the Monash Institute of Pharmaceutical Sciences in Australia published an article on "Nature Metabolism" [1]
    .

    They found that a high-fat diet can damage the mesenteric lymphatic vessels, and the leakage of lymphatic vessels can cause metabolic problems such as abdominal obesity and insulin resistance
    .

    But if the damaged lymphatic vessels are repaired, these metabolic problems can be solved
    .

    This is the first time that lymphatic vessel abnormalities are important in metabolic disorders such as obesity and insulin resistance, and it provides a new therapeutic direction
    .

    The screenshot on the homepage of the paper is correct.
    You read that right.
    The harm of high-fat diet to the intestinal tract is not limited to destroying the intestinal flora.
    This time, you have to pinch the lymphatic vessels
    .

    Lymphatic vessels are an important part of lipid absorption, body fluid homeostasis, and immune monitoring, and are of great significance to the pathogenesis of cancer, inflammation, and neurodegenerative diseases.
    The damage of lymphatic vessel function in peripheral tissues has also been shown to be linked to obesity [2- 5]
    .

    The mesenteric lymphatic vessels are wrapped by visceral adipose tissue (VAT) and are rich in intestinal lipid metabolites and pro-inflammatory mediators[6-7]
    .

    Previous studies have found that diet can change the permeability of mesenteric lymphatic vessels [8], and changes in permeability can allow lymph components to enter the visceral fat tissue [9]
    .

     Cao and her colleagues thought about what these lymphatic vessels would be if they were on a high-fat diet, and whether they would have anything to do with obesity
    .

    They first performed long-term observations on the structure and function of lymphatic vessels, villi and fat-associated lymphatic clusters (FALCs) in mice and humans
    .

    The results found that whether it is a long-term (≥15 weeks) high-fat diet in mice or obese people, the mesenteric lymphatic vessels are disordered, bent, and branched
    .

    Compared with thin people, fat people have about 35% fewer straight lymphatic vessels, and about 50% more curved lymphatic vessels
    .

    Not only that, the lymphatic vessels of mice on a high-fat diet also had leakage, which increased significantly over time, and most of the leakage occurred in highly branched and disordered lymphatic vessels
    .

    b.
    The branches of lymphatic vessels in high-fat diet mice increased significantly; d.
    There were more curved lymphatic vessels in obese people
    .

     In addition, in order to determine whether the damage to the lymphatic vessels is entirely caused by a high-fat diet, or simply because of obesity, Cao and her colleagues have also made further investigations
    .

    They chose obese mice (db/db) with type 2 diabetes and arranged a diet with a normal fat intake for them
    .

    It was found that these mice became obese, and the structure and function of their mesenteric lymphatic vessels were not affected.
    Compared with the lean mice (C57BL/6) on the same normal diet, the number of lymphatic immune cells was equivalent
    .

    Really hammered, Fatty said that this time is very innocent, the pot still has to be carried by a high-fat diet
    .

     I have to say that the high-fat diet has all caught up with the urban transformation, turning the lymphatic vessels from the well-regulated roads into intricate alleys, and the chylomicrons and immune cells that pass by the navigation system have also walked indiscriminately.
    Visceral fat tissue
    .

     It was demolished for you until you didn't even recognize the road to the door of the house! There are thousands of roads, and safety comes first
    .

    Things in this lymphatic vessel go the wrong way, then it is no longer safe
    .

     In in vitro experiments, compared with the control group, the lymph fluid of high-fat diet mice can significantly increase the accumulation of lipid droplets and triglycerides (TGs) in pre-adipocytes (3T3-L1), and make the lipid synthesis-related genes increase The expression is up-regulated to promote the production of fat cells
    .

    Further studies have found that the lymph fluid of mice on a high-fat diet can also cause metabolic problems such as insulin resistance
    .

    Coupled with the leakage of lymphatic vessels, these problems may even develop from local to whole body
    .

    The leakage of the mesenteric lymphatic vessels will really make you fat and your metabolism will be affected
    .

     So what did the high-fat diet do to the mesenteric lymphatic vessels? Cao and her colleagues found that compared with the control group, mice on a high-fat diet and obese people had more active lymphatic endothelial cells and faster lymphangiogenesis
    .

    Once the lymphatic vessels are scratched, incubate a little bit of the lymph fluid under a high-fat diet, and thousands of lymphatic endothelial cells will quickly fill up
    .

    Since it is related to lymphangiogenesis, it is necessary to mention the two signaling pathways COX-2-PGE2 and VEGF-C-VEGFR3
    .

     VEGF-C is an extracellular signaling molecule that can act on lymphatic endothelial cells (LEC) through the receptor VEGFR3 to promote survival, growth and migration
    .

    The COX-2 enzyme synthesizes PGE2 and regulates lymphangiogenesis by recruiting or stimulating macrophages to release VEGF-C [10-11]
    .

     If you want to know the role of these two signal pathways, try blocking the pathways! So Cao and her colleagues chose a COX-2 inhibitor, celecoxib, to treat mice on a high-fat diet and feed them for 15 weeks
    .

    It was found that compared with mice on a normal diet, the levels of VEGF-C in the mesenteric lymphatic vessels of mice on a high-fat diet did increase
    .

    The high-fat diet mice treated with COX-2 inhibitors had significantly lower levels of PGE2 in the mesenteric lymphatic vessels, but the difference in VEGF-C levels was not significant (P=0.
    15)
    .

    Further studies have shown that COX-2 inhibitors can not only effectively alleviate the abnormalities of mesenteric lymphatic vessels caused by high-fat diet, but also alleviate the abnormal glucose metabolism in mice
    .

    It seems that the growth of lymphatic endothelial cells is too "pleasing"
    .

    Throw them away with inhibitors, and the deterrence of a high-fat diet on the lymphatic vessels will be greatly reduced
    .

    The two pathways, COX-2-PGE2 and VEGF-C-VEGFR3, really participate in the remodeling of mesenteric lymphatic vessels by high-fat diet
    .

    Lymphatic vessels: Stop eating, I want to "open"
    .

     The exploration of the mechanism has come to an end, but Cao and her colleagues have a new idea-COX-2 inhibitor seems to be quite practical, can it clean up the mess left by a high-fat diet and reverse the situation? This time they used Cele-Pro, a COX-2 inhibitor that specifically targets lymphatic vessels
    .

    Compared with celecoxib, this Cele-Pro absorbs more than 10 times the amount of mesenteric lymphatics and requires a smaller dose
    .

     A series of studies have found that Cele-Pro can not only reduce the level of PGE2, but also effectively reduce the release of VEGF-C from macrophages, thereby reducing the branching and leakage of lymphatic vessels
    .

    Not only that, it also solves metabolic problems such as insulin resistance caused by lymphatic leakage; it has the effect of reducing weight, but it is not significant
    .

     Cele-pro significantly improves the leakage of lymphatic vessels
    .

    In general, Cao and her colleagues found that a high-fat diet can cause increased branching and leakage of mesenteric lymphatic vessels
    .

    The leakage of lymphatic vessels can cause systemic metabolic disorders such as abdominal obesity and insulin resistance.
    After the use of COX-2 inhibitors that target the mesenteric lymphatic vessels, the damaged lymphatic vessels can be repaired and these metabolic abnormalities can be reversed
    .

    This is the first discovery that the abnormal function of mesenteric lymphatic vessels is a potential factor leading to abdominal obesity and insulin resistance, and it is confirmed that repairing lymphatic vessels can solve these problems, providing a new treatment direction for metabolic disorders and obesity
    .

    After reading this article, Singularity Cake, because of a friend’s birthday party, even ate hot pot and barbecue for two days
    .

    Looking at the white smoke coming out of the pot and the stove, the smell of meat and butter stimulated the sense of smell, and the roasted meat screamed.
    .
    .
    reason, sensibility! Research that even if you do, the mouth still grows on me (tears.
    jpg) References: [1] Cao E, Watt MJ, et al.
    Mesenteric lymphatic dysfunction promotes insulin resistance and represents a potential treatment target in obesity.
    Nat Metab.
    2021 Sep;3(9):1175-1188.
    [2]1.
    Alitalo, K.
    Te lymphatic vasculature in disease.
    Nat.
    Med.
    17, 1371–1380 (2011).
    [3]Petrova, TV & Koh, GY Organ-specifc lymphatic vasculature: from development to pathophysiology.
    J.
    Exp.
    Med.
    215, 35–49 (2018).
    [4]Stacker, SA et al.
    Lymphangiogenesis and lymphatic vessel remodelling in cancer.
    Nat.
    Rev.
    Cancer 14, 159–172 (2014).
    [5]Louveau, A.
    et al.
    CNS lymphatic drainage and neuroinfammation are regulated by meningeal lymphatic vasculature.
    Nat.
    Neurosci.
    21, 1380–1391 (2018).
    [6].
    Raajendiran, A.
    , Tsiloulis, T.
    & Watt, MJ
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