Very interesting video on Jarred Younger's ME/CFS research, thanks for posting it.
Some video highlights:
Timecode 17:30 — Jarred 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.