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CFS severity driven by leptin

Bob

Senior Member
Messages
16,455
Location
England (south coast)
Do we actually know that the increase in leptin is "maladaptive"? Leptin interacts with the hypothalamus to influence endocrine and autonomic function (it is usually described as "satiety" hormone but has actually many functions). Maybe there is a good reason for the increased leptin.

I have been wondering if the leptin increase might be a request for more growth hormone.
In the Pandora webinar Jarred Younger acknowledged that a positive correlation of leptin and fatigue doesn't necessary indicate a cause. In one of his upcoming studies, he's going to test this, by injecting patients with leptin to see if it increases their levels of fatigue. (He says that the effects will be short-lived.) If the fatigue levels are increased with the additional leptin, then he says it may indicate that the leptin levels are pathological.

Edit: Judging from the next few posts, perhaps i've misunderstood something.
 
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Sing

Senior Member
Messages
1,782
Location
New England
Do we actually know that the increase in leptin is "maladaptive"? Leptin interacts with the hypothalamus to influence endocrine and autonomic function (it is usually described as "satiety" hormone but has actually many functions). Maybe there is a good reason for the increased leptin.

I have been wondering if the leptin increase might be a request for more growth hormone.

PS: growth hormone also has other important functions besides making children grow. Low growth hormone alone is enough to cause symptoms that closely resemble milder forms of CFS.

An increase in leptin normally means that a person would not seek to eat. This would be helpful when sick. A lot of animals withdraw, rest and don't eat when sick, which gives them the best chance for recovery. The liver can get to work doing all its detox and other functions apart from having to occupy it so much with processing food.

But--my understanding from Jarred Younger's talk, is that we don't have an unusually high leptin level by itself. Instead there seems to be a problem of activated micoglia which are especially sensitive to leptin, so that even normal fluctuations of leptin will cause extra fatigue and sickness symptoms each time it goes up. Did I understand it right?
 

Sing

Senior Member
Messages
1,782
Location
New England
I also wanted to comment for anyone who hasn't heard the talk given by Jarred Younger that he is very clear and pleasant to listen to, with an organized presentation. He can explain complex things simply and well. I am not surprised that he has impressed other researchers and institutions, including the NIH, to support the directions he wants to take his research. I feel that we have found another good ally in him!
 

Kati

Patient in training
Messages
5,497
I also wanted to comment for anyone who hasn't heard the talk given by Jarred Younger that he is very clear and pleasant to listen to, with an organized presentation. He can explain complex things simply and well. I am not surprised that he has impressed other researchers and institutions, including the NIH, to support the directions he wants to take his research. I feel that we have found another good ally in him!
And I think that the take home message is that there is an interesting correlation between fatigue levels and leptin levels (OMG. I so hate the word fatigue) but more research is needed.
 

Hip

Senior Member
Messages
17,824
Very interesting video on Jarred Younger's ME/CFS research, thanks for posting it.



Some video highlights:

Timecode 17:30Jarred Younger measured the day to day fluctuations in ME/CFS symptoms, and by taking blood samples on the same days, he looked for what changes in the blood correlated to these daily symptom variations. It turns out the only correlation found was between blood leptin levels and fatigue.


Timecode 26:45 — leptin sensitizes microglia. Leptin does not really do anything to microglia cells by itself, but when microglia cells are exposed to inflammatory triggers like LPS (lipopolysaccharide), the inflammatory response from microglia is much stronger if they have been exposed to higher levels of leptin, and what's more, microglia are also triggered into their inflammatory state much more easily after exposure to leptin.

So leptin is both a sensitizer and amplifier of the inflammatory response from microglia (this sensitization of microglia and amplification of microglial response is called microglial priming).


Timecode 28:20 — overview of Jarred Younger's working hypothesis of ME/CFS. His working hypothesis is:

• Some factor initially causes microglia hyper-reactivity (microglial priming) — and there are many environmental or infectious factors that can do this.
• Then once these microglia have become hyper-sensitive, they can over-react to factors present in the body (presumably things like chronic viral infections).


Timecode 30:10 — the strong relationship in 6 out of 10 ME/CFS patients between the day to day fluctuations in fatigue levels, and the day to day variations in leptin levels (the lower the leptin, the lower the fatigue).

Interestingly, a few patients actually showed an inverse relationship between fatigue levels and leptin: for them, the higher the leptin, the lower than fatigue. Jarred Younger says he does not yet have a hypothesis that might explain these inverse relationship cases.


Timecode 49:40 — some speculation by Younger on what may have caused the various ME/CFS epidemics. Younger points out that things like diesel particles in the air (arising from oil fires) can act as an microglia reactivity sensitizers (microglial primers), and this has been shown in rodent models. Younger says that there are many environmental factors that can cause such microglial sensitization, and speculates that the presence of such microglial sensitization factors, in combination with a viral outbreak, may have caused these ME/CFS epidemic outbreaks.
 
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john66

Senior Member
Messages
159
In my case, whatever is attacking the hypothalamus is causing my sleep, weight and energy level. My son was born almost 9 months ago. After a month stay in y he nicu, a very smart genetecist diagnosed him with Prader Willi Syndrome, which occurs on the 15th chromosome and effects the hypothalamus primarily. Lots of research being done with growth hormone and oxytocin. When he was born, he came out floppy, I thought he wasn't alive. I also thought all of his problems were the result of my cfs, the geneticist said he gets his mitochondrial DNA from his mom, so my issues don't cause his.

Later in life paws kids can develop hyperphagia which means the feedback loop saying I'm full doesn't exist. There is a drug, that is an analog of pot, that lowers appetite. I'm hoping left in finds its way into the research. Primarily research is being done at Vanderbilt University, University of Florida, Michigan and Winthrop University. Lots of research, some big money because of obesity and I hope and pray they find a cure for PWS and that lots of that same research can help cure or augment what is lacking in the cfs world
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
In my case, whatever is attacking the hypothalamus is causing my sleep, weight and energy level. My son was born almost 9 months ago. After a month stay in y he nicu, a very smart genetecist diagnosed him with Prader Willi Syndrome, which occurs on the 15th chromosome and effects the hypothalamus primarily. Lots of research being done with growth hormone and oxytocin. When he was born, he came out floppy, I thought he wasn't alive. I also thought all of his problems were the result of my cfs, the geneticist said he gets his mitochondrial DNA from his mom, so my issues don't cause his.

Later in life paws kids can develop hyperphagia which means the feedback loop saying I'm full doesn't exist. There is a drug, that is an analog of pot, that lowers appetite. I'm hoping left in finds its way into the research. Primarily research is being done at Vanderbilt University, University of Florida, Michigan and Winthrop University. Lots of research, some big money because of obesity and I hope and pray they find a cure for PWS and that lots of that same research can help cure or augment what is lacking in the cfs world

Very sorry to hear that your son has Prader Willi Syndrome. That is hard to deal with - for him and for you.