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Fat cells, Leptin and the Production of CD4 T-cells for AIDS Patients


Cal Crilly

Fat cells make a hormone called leptin.

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

In detail ...

“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


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

Anorexic girls get immune failure from lack of fats cells to make their leptin so this drug can replace leptin action while avoiding the carbs and avoiding the ARV's as an alternative.

"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.


You also don't want to get too obese or diabetic as opposed to skinny because then you can get 'leptin resistance' like 'insulin resistance' and immune failure and this is also seen in diabetics.

Plus gastric cells are leptin releasing so if you don't get hungry then no leptin will be made 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.


This study is too new it is not online, the name says it all (: get fat to raise t-cells

Immunometabolism: CD4+ T cell activation by adipocytes in obesity


So eat fish and chips more

Now this is really important to note.

The level of CD4 T-cells in guys on Antiretrovirals went up if they were fat and down if they were skinny so ARV's still made no difference in skinny people tagged HIV.

It means again your body mass is more important to raise t-cells.

"Relative to men with a normal BMI, overweight and obese men had increases at week 144 that were 35 and 113 cells/mm3 higher, respectively, while underweight men
had CD4+ T-lymphocyte increases that were 94 cells/mm3 lower."

Body Mass Index and CD4+ T-Lymphocyte Recovery in HIV-Infected Men with Viral
Suppression on Antiretroviral Therapy


I think this also explains why perfectly healthy people can have low T-cells, in fact fitness junkies are at the most risk because they have hardly any fat cells to make leptin.

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

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


While the use of antiretrovirals to do all this always was questionable from the beginning because people may have had raised T-cells on ARV's but they died at the same rate.

"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



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