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Leptin
Andrew Gladman reflects upon the recent IACFS/ME conference and the buzz surrounding a small molecule, leptin.
Discuss the article on the Forums.

CFS severity driven by leptin

Discussion in 'Latest ME/CFS Research' started by MeSci, Apr 11, 2013.

  1. MeSci

    MeSci Activity level: 6

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  2. jeffrez

    jeffrez Senior Member

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    This looks really good, as close to a biomarker as we have so far. I'd like to know to what extent leptin and whatever cytokines are involved are related to HPAA function.
    rosie26 and snowathlete like this.
  3. jeffrez

    jeffrez Senior Member

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    Ask and you shall receive. :D

    Ann N Y Acad Sci. 2000;917:647-57.
    Cytokines, leptin, and the hypothalamo-pituitary-adrenal axis.

    Gaillard RC, Spinedi E, Chautard T, Pralong FP.
    Source

    Division of Endocrinology, Diabetology and Metabolism, Department of Medicine, University Hospital (CHUV), CH-1011 Lausanne, Switzerland. Rolf-Christian.Gaillard@chuv.hospvd.ch
    Abstract

    The endocrine and immune systems are linked via an elaborated communication system constituted by an array of cytokines and neuropeptides which interact to modulate the integrated response of an organism to infection. Weight loss and anorexia, probably secondary to cytokine release, frequently accompany infection, but leptin could also play a role. Like cytokines, leptin serves as a peripheral messenger to convey signals to the brain. Expression of leptin is stimulated by glucocorticoids, endotoxins, and cytokines; on the other hand, leptin seems to inhibit the activation of the hypothalmo-pituitary-adrenal (HPA) axis. Indeed leptin exerts a direct, dose-dependent inhibition of stimulated cortisol secretion by normal human and rat adrenal cells in vitro. These effects are mediated by the long isoform of the leptin receptor, because its transcript is expressed in the adrenal tissue. In addition we investigated the role played by the glucocorticoids in the development of tolerance of the hypothalamo-corticotropic, immune and adipose system responses to repeated endotoxin administration. Unlike that of the corticotropic axis, tolerance of the immune and adipose systems is at least partially glucocorticoid-independent. This crosstalk between the endocrine, immune, and adipose systems may be of prime importance to homeostasis in pathophysiological events occurring during infection.


    -----
    So let's block the leptin, and figure out how to negatively modulate whatever cytokines are getting upregulated. Seems that possibly could provide some symptom relief, at least, if not induce a functional recovery in best case scenario.
    GracieJ, Antares in NYC, Sing and 4 others like this.
  4. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    this looks alot like what dr jack kruse is doing by improving leptin resistence and circadian rhthyms etc using low carb diets, adrenal hormones and cycloset. Some of his stuff is abit out there but there is plenty of other info thats easy to understand. http://www.jackkruse.com/blog-index/

    cheers!!!
    jeffrez, dece and MeSci like this.
  5. Dreambirdie

    Dreambirdie work in progress

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    Leptin....really? Who would have thunk it was associated with endocrine and immune response. As always, though, it's a complex series of reactions that are involved.

    I imagine that leptin, (the appetite suppressing hormone) would go up when the body is in crisis. But doesn't cortisol, (the stress hormone) go up as well? From what is indicated here, leptin brings the cortisol down. So blocking it would increase cortisol, which might not be a good thing.
    leela likes this.
  6. Valentijn

    Valentijn Activity Level: 3

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    I don't think leptin will provide a biomarker:
    So leptin levels aren't abnormal, but there is some indication that fluctuations in these normal levels are correlated to symptoms in ME/CFS patients. Basically it looks like it's a link in the causation chain.
    Simon likes this.
  7. lnester7

    lnester7 Seven

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    I get sooo hungry when tired, and tend to do binge eating.
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  8. jeffrez

    jeffrez Senior Member

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    Nevertheless, there's a high correlation between leptin levels and fatigue in PWCs that does not exist in normals. And it's not known yet whether it's a link in the chain, or whether the leptin itself is the cause:

    Like I said, this seems as close to a possible biomarker as we've gotten so far. It's a great start down what could be a very promising road. Being able to predict fatigue severity close to 80% is pretty amazing, not to mention perhaps a possible future treatment reducing fatigue just by blocking or modulating leptin or leptin receptor sensitivity somehow, if it's the leptin itself that proves to be the causal factor. Big bravo to Montoya et al. Really great work so far.
    leela and rosie26 like this.
  9. Gijs

    Gijs

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    This finding does say nothing at all. First under the current terminology leptin is not appropriately considered adipokines (cytokines) as they do not act on the immune system. Often, this peptide (leptin) is referred to as adipokines, however it can be more accurately put into the larger, growing list of adipose derived hormones. This is not a usefull marker and say nothing about the role of cytokines in the pathophysiology of CFS, simply because leptin is no cytokine.
  10. MeSci

    MeSci Activity level: 6

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    From a quick look that site looks pretty good.
  11. Hip

    Hip Senior Member

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    The reason that elevated leptin levels increase fatigue in ME/CFS is possibly related to the fact that leptin causes microglial cells in the brain to release the cytokine IL-6 (reference: 1), and when IL-6 was experimentally injected into healthy men, it caused fatigue and a reduced capacity to concentrate (reference: 1).
    rosie26, Sing, Iquitos and 6 others like this.
  12. jeffrez

    jeffrez Senior Member

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    Have to disagree. It's a significant finding, one that possibly could lead to actual or functional mechanisms.

    Contrib Nephrol. 2006;151:151-64.
    Leptin as a proinflammatory cytokine.

    Lord GM.
    Source

    Department of Nephrology and Transplantation, 5th Floor Thomas Guy House, King's College London, Guy's Hospital, London, UK. Graham.lord@kcl.ac.uk
    Abstract

    Leptin is a 16-kDa protein produced mainly by adipocytes. Animal models demonstrate that leptin is required for control of bodyweight and reproduction, since mice defective in leptin or the leptin receptor are obese, hyperphagic insulin resistant and infertile. Our initial series of observations lead us to propose that leptin also had significant effects on human type I proinflammatory immune responses. In support of this hypothesis, leptin deficient mice are resistant to a wide range of autoimmune diseases and display features of immune deficiency. Subsequent work has confirmed that leptin has a pleiotrophic role on the immune response and can rightly be considered, both structurally and functionally, as a proinflammatory cytokine.
    NK17, Iquitos, rosie26 and 3 others like this.
  13. Hip

    Hip Senior Member

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    Iquitos, leela, rosie26 and 3 others like this.
  14. Tristen

    Tristen Senior Member

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    IL6 levels is the one immune marker that with changes, most immediately affects my symptoms. The rest all seem to change later.
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  15. adreno

    adreno 3% neanderthal

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  16. dannybex

    dannybex Senior Member

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    I don't get it either. Leptin suppresses appetite, and yes, mine's been suppressed for a good 10-11 years now (out of 14-15 years sick), and so I need to take supplemental HCL in order to increase protein digestion and stomach motility. But I'm also skinny as a stick. What about the patient population who may be overweight or even obese?
  17. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    i think a part of the issue they are trying to achieve with improving leptin is fatloss but also its said that this increased body fat increases inflammation which increases fatigue, also reduces insulin sensitivity and affects sex hormones etc and turns into a viscious circle. Generally those with alot of weight are leptin resistent(insulin resistent) because of the excess weight. I think dr jack kruse who is pushing alot of these points is mainly aimed at people in poor health due to life style factors, stress etc but not directly aimed at cfs/me, so i think we have to take his theories and twist it to suit us individually.
  18. Ema

    Ema Senior Member

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    Tristen likes this.
  19. Tristen

    Tristen Senior Member

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    Thanks Ema
  20. dbkita

    dbkita Senior Member

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    I think there are many ways to arrive at hpaa dysfunction.
    Mine were completely wrecked with an autoimmune disease but my leptin was undetectably low. While the study is interesting my guess us it is not part of the source but a link in the chain that fails. I would bet the immune system trumps leptin signaling, just like it trumps thyroid levels via rt3 or adrenal steroid genesis given enough time.
    Sing, merylg, Rolo and 1 other person like this.

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