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.

The graph on the left is from a 1984 paper of mammalian hibernation. It showed that melatonin – a gene under circadian control – has a circadian pattern in the summer but is totally squelched in the winter. The graph on the right is from a Nature paper from 2018 showing that activating the AhR squelches the expression levels of circadian controlled 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.

Red and light blue lines are kynurenine levels of mice with normal sleep. Purple are mice with disrupted sleep drinking water. Turquoise is mice with disrupted sleep drinking Pu Erh tea. Kynurenine levels are largely restored.

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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2 thoughts on “Torpor, Circadin Rhythms and the AhR: Obesity Explained, Episode 4”

  1. Hi Brad,

    I’m curious if you think that Pu’ Erh Tea needs to be taken after meals to be effective.

    I’ve been drinking it first thing in the morning and eating a late afternoon/early evening OMAD most days. Unfortunately, I’m caffeine sensitive, so i don’t mess with tea or coffee after noon.

    I usually don’t get hungry during the day (I’m the sort of glutton who eats so much that even eating once a day i have trouble losing weight), and even if i did, it’s pretty hard to find quick, easy food that’s low in PUFA. It’s easier for me to avoid PUFA by making everything from scratch at home.

    I’ve been messing around with different ideas from this blog and the Ray Peat forums and i keep yo-yoing. Been losing and gaining the same 15 pounds sonce January 2022.

    I drink black Pu’ Erh Tea (a 16 ounce cup made with 3 tbsp of loose leaf) every morning… Sometimes i have coffee after, but not every day. Sometimes, i have coconut oil before my tea, but not always.

    Do you have any ideas that may help?
    Are you still using pyruvate and l-carnitine (if so, are you still steadily dropping weight)?

    I’ve previously tried ALA supplements and stearic acid. Neither seemed to make any difference.

    Any advice on which supplements you sell/advocate using would work best for my situation?

    1. George, how are you making your tea?

      I make mine like this, I get up at 6 and put a kettle on, then put my loose leaf in a one of those tea balls that has the chain and hook. I pour my hot water into a 20oz mug, drop the ball in, and put the top on. I let it steep from about 6:10 to 8:30-9ish. Sometimes I’ll drink it black, but usually I put a dash of pure stevia and some half n half or heavy cream. Pretty good coffee replacement this way. So even if it’s not the ideal meal timing I feel I am still better off than drinking coffee. I can’t drink it at night either, but it is pretty good cold too.

      Feel you on the weight, dropped 20lbs this summer, and put about 15 back on by New Years. I’ve just come to the conclusion that getting my metabolism back on track at 47 is not going to be something that happens over night, or even in a year. Even with Brad’s excellent biohacking supplements and advice I don’t know if I’ll ever get to where I would be if I had grown up in a world without excess linoleic acid. I just try to get a little better every day and be diligent with my calories by making sure I’m getting sufficient nutrition and staying in a deficit. Maybe one day I’ll get to that holy grail of 4000 calories a day and staying trim. I believe it can be done, even at my age, but slow and steady wins the race.

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