Torpor, Circadin Rhythms and the AhR: Obesity Explained, Episode 4

Episode 4 of Obesity Explained is out!

Watch The Video!

Video Summary

It’s January. Days are short, the light is dim. This one is about circadian rhythms, daylength, body weight and torpor.

My working hypothesis is that the Aryl Hydrocarbon Receptor is A, if not THE, master regulator of torpor. Kynurenine is a tryptophan metabolite that is elevated in hibernating mammals during the fattening stage of their yearly cycle. Kynuernine is elevated to a similar extent in obese humans.

An elevated AhR shifts your metabolism into a torpor-like state that favors fat storage. One of the ways it does this is by shutting down circadian rhythms. The AhR is closely related to the CLOCK gene – the transcription factor that controls circadian rhythms. Transcription factors are genes that control the expression of other genes. When activated, the AhR displaces the CLOCK gene at the site of the DNA where clock would normally attach and turn on genes that have a circadian rhythm. The AhR blocks transcription of these genes.

NAD+ levels are controlled in a Circadian fashion. The enzyme NAMPT recycles NAD+ after it is converted to nicotinamide by NADase enzymes like the sirtuins, PARPs and CD38. Mice lacking the CLOCK gene – the very gene displaced by an activated AhR – have very low levels of NAD+ and become very fat.

Humans with a less active version of the clock gene experience weight loss stall on a low calorie diet.

Theabrownin and Pu Erh Tea

Pu Erh tea is a fermented tea that has a high quantity of dark brown pigments called theabrownin (brown pigment from tea). The tea and theabrownin reverse the effects of a dysregulated circadian rhythm, probably by inhibiting the AhR and thus lowering kynurenine levels. Kynurenine and the AhR are regulated in a positive feedback loop. The AhR upregulates an enzyme called IDO1 which creates kynuerenine which activates the AhR. Pu Erh tea breaks this loop.

I present evidence in the video that the mechanism of action of Pu Erh tea is likely that theabrownin is a direct inhibitor of the AhR.

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