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Inhibition Of Peripheral Serotonin Production Protects From Diet-induced Obesity And Related Complic

Discussion in 'Scientific Studies' started by Waremu, Mar 22, 2015.

  1. Waremu

    Waremu Member

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    Don't known if someone has already mentioned this recent news from this particular study here already or not, but definitely another point for Dr. Ray Peat.

    "Obesity is a major risk factor for chronic disease. A new study in mice reveals that lowering levels of the signaling molecule serotonin outside of the brain reduces obesity and its complications by increasing brown adipose tissue (BAT) energy expenditure."

    "Tryptophan (Trp) is converted into serotonin (5-HT) within the brain by the enzyme tryptophan hydroxylase (TPH)2, where it both increases sympathetic nervous system signaling to brown adipose tissue (BAT) and suppresses appetite. In the gastrointestinal tract (GIT), Trp is converted to serotonin by the enzyme Tph1. Crane et al.6 find that reducing circulating serotonin by inhibition of Tph1 or deletion of the Tph1 gene increases the sensitivity of BAT cells to noradrenaline (NA) and β-adrenergic receptor (β-AR) signaling. This drives thermogenesis by fat and glucose oxidation via the actions of Ucp1. Sustained thermogenesis recruits additional fat and glucose from peripheral tissues for oxidation by BAT cells, which reduces fat storage in WAT as well as in undesirable locations such as skeletal muscle and the liver, thereby providing protection against obesity, skeletal muscle insulin resistance and NAFLD."


    http://www.nature.com/nm/journal/v21/n2 ... .3797.html
     
  2. RPDiciple

    RPDiciple Member

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    i saw it but i dont think it was on this forum. Its great
     
  3. Such_Saturation

    Such_Saturation Member

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    Next thing they will say is that being the happiness hormone, being too happy can lead to fatness and diabetes. We need to suffer to be healthy, it's just the way god wills it, you guys.
     
  4. haidut

    haidut Member

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    It is posted on the forum (several months ago), we discussed what drugs would work to achieve this effect. I posted a study on vitamin D inhibiting TPH-2 but the doses required to do it are very high. Something like mianserin or ketanserin may work better but would work differently than what the study recommends.
     
  5. OP
    Waremu

    Waremu Member

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    Thanks. I usually catch the stuff you post, but guess I dont remember seeing your post on it. Good to see the study nevertheless.
     
  6. paymanz

    paymanz Member

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    [ moderator edit: threads merged ]

    Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. - PubMed - NCBI

    Abstract

    Mitochondrial uncoupling protein 1 (UCP1) is enriched within interscapular brown adipose tissue (iBAT) and beige (also known as brite) adipose tissue, but its thermogenic potential is reduced with obesity and type 2 diabetes for reasons that are not understood. Serotonin (5-hydroxytryptamine, 5-HT) is a highly conserved biogenic amine that resides in non-neuronal and neuronal tissues that are specifically regulated via tryptophan hydroxylase 1 (Tph1) and Tph2, respectively. Recent findings suggest that increased peripheral serotonin and polymorphisms in TPH1 are associated with obesity; however, whether this is directly related to reduced BAT thermogenesis and obesity is not known. We find that Tph1-deficient mice fed a high-fat diet (HFD) are protected from obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD) while exhibiting greater energy expenditure by BAT. Small-molecule chemical inhibition of Tph1 in HFD-fed mice mimics the benefits ascribed to Tph1 genetic deletion, effects that depend on UCP1-mediated thermogenesis. The inhibitory effects of serotonin on energy expenditure are cell autonomous, as serotonin blunts β-adrenergic induction of the thermogenic program in brown and beige adipocytes in vitro. As obesity increases peripheral serotonin, the inhibition of serotonin signaling or its synthesis in adipose tissue may be an effective treatment for obesity and its comorbidities.
     
  7. Mountain

    Mountain Member

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    I prefer this title over that of the study's
     
  8. Momado965

    Momado965 Member

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    Can lisuride work?
     
  9. haidut

    haidut Member

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    Dopamine agonists inhibit TPH, so theoretically yes.
     
  10. Momado965

    Momado965 Member

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    Sounds like metegoline is way better since its a pure serotonin antagonist. Am I right?
     
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