“Food for thought: an endogenous ligand of Rev-erb is heme (the iron-binding element in red blood cells). Heme is degraded into bilirubin. Elevated levels of bilirubin cause jaundice. A treatment of neonatal jaundice is exposure to blue light. Blue light is a major regulator of circadian rhythms and Rev-erb is an executive-level player in this game. The primary mechanisms of blue light appear unrelated in these two models (melanopsin activation vs. bilirubin photoisomerization), but seem intertwined, because heme activates Rev-erb. Cool.” (From HERE)
"Pharmaceutical-grade circadian augmentation = unwittingly better-timed meals? Improved body composition? …they were eating more and moving less. ... One possible mechanistic explanation comes from mice lacking Rev-erb in skeletal muscle (Woldt et al., 2013). Mitochondrial biogenesis was impaired and exercise tolerance was reduced in these mice. Spontaneous physical activity was lower; thus, it stands to reason that Rev-erb agonism may improve skeletal muscle mitochondrial function. This isn’t entirely consistent with the drug study, but pretty close." (From HERE)
REV-ERB is really really good for skeletal muscle.
Well, so does REV-ERB alpha! In a new study, knocking down REV-ERB alpha jacked up NLRP3 and pharmacologically enhancing it attenuated NLRP3 (Pourcet et al., 2017). The consequence of this in REV-ERB KO mice injected with LPS was hyper-inflation. No bueno. Mice given the commercially-available REV-ERB alpha agonist "Stenabolic" were protected.
Interestingly, Stenabolic has been touted as exercise in a bottle, which is consistent with predictions and the mouse studies. Cool.
I'm geeking out about REV-ERB alpha & SR9009. And fwiw, I don't think anything will actually fully replace the benefits from actual physical activity and/or exercise, although it's very hard for some people; eg, COPD, CHD, etc. In those populations, if they can't exercise enough to really improve their condition, something like this might help. But I'm sure perfectly healthy people are going to try it. If you do, let us know in the comments!
"Rev-erb agonism may improve skeletal muscle mitochondrial function."
Regulation of Circadian Behavior and Metabolism by Synthetic Rev-erb Agonists (Solt et al., 2013)
Rev-erb alpha modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy (Woldt et al., 2013)
While you could opt for the OTC supplemental route to augment REV-ERB alpha and essentially get to eat more, move less, and still improve health, you could also do it by improving your circadian hygiene. The easy steps: breakfast & sunlight in the morning, darkness or blue blockers at night. Voila!
After the SERcadian Rhythms post, some people started taking the serine-containing supplement "Seriphos" and reported positive effects on sleep. I have a feeling that Stenabolic may be similarly effective, particularly for people with poor circadian hygiene.
UPDATED Affiliate links: still looking for a pair of hot blue blockers? Carbonshade is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. TrueDark and BLUblox.
If you have no idea what I’m talking about, read this then this.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.