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Fat Cells make Leptin and T-cells?

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Cal Crilly

Fat Cells make Leptin and T-cells

Fat cells make a hormone called leptin which allows t-cells to be made.

If you have no fat cells then leptin disappears because it is the adipocytes or fat cells that make it.

In detail using poor mice...

“Nutritional deprivation suppresses immune function. The cloning of the obese gene and identification of its protein product leptin has provided fundamental insight into the hypothalamic regulation of body weight.

Circulating levels of this adipocyte derived hormone are proportional to fat mass but maybe lowered rapidly by fasting or increased by inflammatory mediators.

The impaired T-cell immunity of mice now known to be defective in leptin (ob/ob)4 or its receptor (db/db) has never been explained.

Impaired cell-mediated immunity and reduced levels of leptin are both features of low body weight in humans.

Indeed, malnutrition predisposes to death from infectious diseases.

We report here that leptin has a specific effect on T lymphocyte responses, differentially regulating the proliferation of naive and memory T cells.

Leptin increased Th1 and suppressed Th2 cytokine production.

Administration of leptin to mice reversed the immunosuppressive effects of acute starvation.

Our findings suggest a new role for leptin in linking nutritional status to cognate cellular immune function, and provide a molecular mechanism to account for the immune dysfunction observed in starvation.”

Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression

http://life.nthu.edu.tw/~b861662/leptin.pdf

There's a hormone mimic on the market now called Metreleptin or Myalept.

Anorexic girls get immune failure from not having enough fats cells to make their leptin so this drug can replace leptin and restores their immune function back to normal.

"Our data show that metreleptin administration, in doses that normalize circulating leptin levels, induces transcriptional changes, activates intracellular signaling pathways, and restores CD4(+) T-cell counts.

Thus, metreleptin may prove to be a safe and effective therapy for selective CD4(+) T-cell immune reconstitution in hypoleptinemic states such as tuberculosis and HIV infection in which CD4(+) T cells are reduced."

Selective capacity of metreleptin administration to reconstitute CD4+ T-cell number in females with acquired hypoleptinemia.

http://www.ncbi.nlm.nih.gov/pubmed/23382191

Gastric cells also release leptin so if you don't get hungry or eat then leptin won’t be made in the gut and there will be no t-cells via the gastric mechanism, so much of this is about eating…

"Leptin is a hormone that plays a central role in the regulation of food intake and energy expenditure.

Originally discovered in mature white adipocytes, it was subsequently isolated from the gastric mucosa. This tissue contains a large number of epithelial endocrine and exocrine cells secreting leptin in the blood stream and in the gastric lumen, respectively."

Leptin secretion by white adipose tissue and gastric mucosa.

http://www.ncbi.nlm.nih.gov/pubmed/17149693

You also don't want to be too obese or diabetic as opposed to skinny because then you can get 'leptin resistance' which is similar in some ways to 'insulin resistance'.

Leptin resistance leads to less t-cells to do the work of opening up arteries, immune failure also results and this is seen in diabetics who get arterial collapse, sepsis and gangrene at the end stage.

This is the effect of leptin resistance in obese children and the effect on t-cells when given leptin.

“Leptin deficiency was associated with reduced numbers of circulating CD4+ T cells and impaired T cell proliferation and cytokine release, all of which were reversed by recombinant human leptin administration.”

Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC150795/

These fat and t-cell studies are from heart research papers.

Immunometabolism: CD4+ T cell activation by adipocytes in obesity

http://www.nature.com/nri/journal/v13/n4/pdf/InBrief.pdf?WT.ec_id=NRI-201304

Fats are key to immune activation.

“All identified fatty acids were able to individually enhance T-cell proliferation.

These data indicate that adipocytes can modulate CD4(+) T-cell function through the release of lipids.

Remarkably, free fatty acids were the most prominent modulators of T-cell proliferation, possibly leading to an accumulation of these cells in adipose tissue.”

Adipocyte-derived lipids modulate CD4+ T-cell function.

http://www.ncbi.nlm.nih.gov/pubmed/23504601

This also explains why perfectly healthy people can have very low t-cells, fitness junkies are quite at risk of getting low t-cell counts because they have hardly any fat cells to make leptin and often avoid fatty foods.

“Prolonged strenuous exercise is followed by a temporary functional immune impairment.”

Strenuous exercise decreases the percentage of type 1 T cells in the circulation

http://www.jappl.org/content/91/4/1708.full

Now this is important to note for people on antiretroviral drugs.

The level of CD4 T-cells in guys on anti-retrovirals (ARV’s) went up far more if they were fat.

It means your body mass is more important to raise t-cells than the drugs.

"BMI predicts CD4+ T-lymphocyte gains in men started on ART.”

CD4+ T-Lymphocyte Recovery in HIV-Infected Men with Viral Suppression on Antiretroviral Therapy
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342850/

Again, this recent study showed low leptin was the key factor that affected t-cells in people on HAART.

“Serum leptin levels were significantly higher in patients with high CD4 counts than in patients with low CD4 counts"

And they concluded that HAART wasn’t helping leptin levels or t-cells.

"Conclusion: Serum leptin level was higher in HIV patients with high CD4 count and correlated with fasting serum insulin and HOMA-IR, thereby indicating that HAART treatment could lead to decreased levels of leptin in HIV patients, which might lead to impaired immunological recovery."

Relationship between Leptin Levels and Suppressed CD4 Counts in HIV Patients

http://www.researchgate.net/publication/227856818_Relationship_between_Leptin_Levels_and_Suppressed_CD4_Counts_in_HIV_Patients

The use of antiretrovirals to raise t-cells was always questionable from the beginning because people may have had a small rise in t-cells on ARV's but they died at the same rate from poisoning, especially with the AZT dose between 1987 and the mid 90’s before HAART lowered the dose.

"The results of Concorde do not encourage the early use of zidovudine in symptom-free HIV-infected adults. They also call into question the uncritical use of CD4 cell counts as a surrogate endpoint for assessment of benefit from long-term antiretroviral therapy."
Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection 1994
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(94)90006-X/abstract

So who is going to put up their hand and ask their doctor about measuring their leptin and trying out Myalept when the doctor says HAART might work?

http://www.myalept.com/

Back in the 80’s everyone demanded the government give them AZT and that got everybody nowhere and killed a lot of people, tell your doctor about leptin instead and make them think outside the box.

Or do something about this so people in Africa get some food and get their t-cells back.

“A five-year study by the University of Cape Town's African Food Security Unit Network has exposed a food crisis that constitutes a "death sentence" for many and which the government has labelled as "serious".”

12 Million Going To Bed Hungry in SA

http://www.timeslive.co.za/thetimes/2013/01/30/twelve-million-going-to-bed-hungry-in-sa  TAGS:undefined


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