Leptin's role in MS - another step in the process

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Leptin's role in MS - another step in the process

Postby CaveMan » Wed Apr 17, 2013 3:33 pm

Searching around Leptin info, found these studies which may be of interest.
First three are MS related specifically and last two links are more about Leptins role in the immune system.
Basically Leptin is a major regulator in the Immune system,
low leptin levels - low innate immune activity - high risk of infections.
high leptin levels - high adaptive immune activity - high risk of autoimmune conditions.

Researchers have seen a link between high leptin levels and MS in both diagnosis and relapses, they have suggested that it may be a therapeutic target in MS treatment, i.e. drug intervention to lower leptin levels.
I think they have the wrong end of the stick, the goal should be to determine the cause of elevated leptin levels.
Leptin is a relatively new hormone, discovered in 1994, but in this time it has had a rapid rise to stardom where many are now refering to it as the master hormone controlling the entire endochrine system, this makes sense in some ways when you consider it is produced by adipose tissue (fat cells) and these are reflective of net energy balance in the body and net energy balance is the primary predicter of survival through difficult times, so it is a very primal driver.

From what I have read leptin resistance (high leptin) precedes insulin resistance (high insulin) by decades very often and high blood glucose precedes insulin resistance in the same way.

Review of data rom the Framingham study, although the study failed to prove it's hypothesis to link high cholesterol to CVD risk, it did gather an imense amount of data that researchers are still disecting today, one of the key findings from this data was:
Conclusions
Blood glucose, even within the normal range, is a strong independent predictor of 2-year all-cause, CVM,
and non-CVM in nondiabetic subjects with CVD and therefore of prognostic significance for these high-risk patients.

http://www.math.ucla.edu/~scp/publicati ... tality.pdf
I couldn't find the review I was looking for, but it determined that high normal blood glucose predicted all cause mortality risk decades in advance for even those without any signs of disease.

From my readings there are two primary contributers to systemic inflamation and hence the environment for chronic disease to manifest.
[*] Excessive carbohydrate consumption, particularly High GI foods, like white flowers, processed sugar, soda etc.
[*] Excessive consumption of Omega 6 (Vegetable and Seed oils)

As Leptin is likely the first hormone in the cascade to go out of whack as our health declines, it will most likely also be the last to fall back in line. Get everything else in your life (diet, lifestyle, stress behaviour) right and let your body do the healing.

The consumption of both of these have risen at exponential levels in the last 50 years in the western world and this corrolates strongly with the declarations of chronic disease epidemics we see on the news every night.

http://www.ncbi.nlm.nih.gov/pubmed/12799033
Leptin as a marker of multiple sclerosis activity in patients treated with interferon-beta.
Batocchi AP, Rotondi M, Caggiula M, Frisullo G, Odoardi F, Nociti V, Carella C, Tonali PA, Mirabella M.
Institute of Neurology, Catholic University, Largo Gemelli 8, 00168, Rome, Italy. annapaola_b@hotmail.com
Abstract
The role of leptin was investigated in relapsing-remitting multiple sclerosis (MS). Control and MS patients showed comparable baseline serum leptin levels. During the first year of IFNbeta-1a treatment, leptin significantly decreased since 2 months after starting therapy in 11 patients who had no relapses. A significant decrease in IL12/IL10 ratio was observed in this group of patients only after 1 year of treatment. An increase of leptin was observed before the first clinical exacerbation in 13 relapsing patients. Leptin may play a pathogenic role in MS and can be a useful marker of disease activity and response to therapy.


http://www.ncbi.nlm.nih.gov/pubmed/20606678
Leptin as a metabolic link to multiple sclerosis.
Matarese G, Carrieri PB, Montella S, De Rosa V, La Cava A.
Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), Via S. Pansini 5, 80131 Napoli, Italy. gmatarese@napoli.com
Abstract
Clinical and experimental data, together with epidemiological studies, have suggested that the pathogenesis of multiple sclerosis (MS) might involve factors that link the immune system with metabolic status. Moreover, recent research has shown that leptin, the adipocyte-derived hormone that controls food intake and metabolism, can promote experimental autoimmune encephalomyelitis, an animal model of MS. In patients with MS, the association of leptin with disease activity has been dissected at the molecular level, providing new mechanistic explanations for the role of this hormone in MS. Here, we review the intricate relationship between leptin and other metabolic modulators within a framework that incorporates the latest advances linking the CNS, immune tolerance and metabolic status. We also consider the translational implications of these new findings for improved management of MS.


http://www.pnas.org/content/102/14/5150.short
Leptin increase in multiple sclerosis associates with reduced number of CD4+CD25+ regulatory T cells
Giuseppe Matarese*,†,‡, Pietro Biagio Carrieri§, Antonio La Cava¶, Francesco Perna∥, Veronica Sanna*,†, Veronica De Rosa*,†, Daniela Aufiero*,†, Silvia Fontana*, and Serafino Zappacosta†
Author Affiliations
Edited by Laurie H. Glimcher, Harvard School of Public Health, Boston, MA, and approved February 10, 2005 (received for review December 3, 2004)
Abstract
We analyzed the serum and cerebrospinal fluid (CSF) leptin secretion and the interaction between serum leptin and CD4+CD25+ regulatory T cells (TRegs) in naïve-to-therapy relapsing-remitting multiple sclerosis (RRMS) patients. Leptin production was significantly increased in both serum and CSF of RRMS patients and correlated with IFN-γ secretion in the CSF. T cell lines against human myelin basic protein (hMBP) produced immunoreactive leptin and up-regulated the expression of the leptin receptor (ObR) after activation with hMBP. Treatment with either anti-leptin or anti-leptin-receptor neutralizing antibodies inhibited in vitro proliferation in response to hMBP. Interestingly, in the RRMS patients, an inverse correlation between serum leptin and percentage of circulating TRegs was also observed. To better analyze the finding, we enumerated TRegs in leptin-deficient (ob/ob) and leptin-receptor-deficient (db/db) mice and observed the significant increase in TRegs. Moreover, treatment of WT mice with soluble ObR fusion protein (ObR:Fc) increased the percentage of TRegs and ameliorated the clinical course and progression of disease in proteolipid protein peptide (PLP139–151)-induced relapsing-experimental autoimmune encephalomyelitis (R-EAE), an animal model of RRMS. These findings show an inverse relationship between leptin secretion and the frequency of TRegs in RRMS and may have implications for the pathogenesis of and therapy for multiple sclerosis.


http://www.hindawi.com/journals/mi/2010/568343/
http://www.cmi.ustc.edu.cn/4/1/1.pdf
I am just an interested individual trying to crack the autoimmune nut.
Partner has Graves Disease, 5 years, showing good test results, looking forward to potential remission in the near future.
3 friends have MS, 1 just recently diagnosed, severity 7/10.
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Re: Leptin's role in MS - another step in the process

Postby Leonard » Wed May 01, 2013 7:26 am

great info, at the core of the issue
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