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You've given me a chance to put some useless information to use, oh boy! So the article mentions GLP-1, but the primary hormones responsible for hunger and sat

You've given me a chance to put some useless information to use, oh boy! So the article mentions GLP-1, but the primary hormones responsible for hunger and satiety are leptin and ghrelin. Leptin is an anorexic hormone that is produced by adipose tissue. It regulates metabolism, particularly resting/basal metabolic rate. An interesting thing that you'll find with bodybuilders and competetive athletes, is that when you cross into single-digit bodyfat, it becomes significantly more difficult to continue to lose fat. Some people attribute this to a phenomena known as "adaptive thermogenesis", which is the idea that your metabolism adapts and regulates itself based on your lifestyle and environmental factors, so that you don't continue either losing/gaining weight forever. But the major contributing factor is that with diminished adipose tissue, systemic production of leptin is severely reduced and this lowers both metabolic rate and lipolysis. (You can artificially restore leptin production and re-induce lipolysis in a low-bodyfat state through a short window (~36 hours) of carbohydrate overfeeding) On the other side of the coin, you have Ghrelin. Ghrelin is a peptide produced in the stomach, and is pretty solely involved in appetite stimulation. If you've ever taken GHRP (Growth-Hormone-Releasing-Peptide) or Ibutamoren Mesylate (oral growth hormone secretagogue), It will drive you ravenously hungry. A side effect of the peptides/hormones many athletes take for growth hormone production is the release of Ghrelin and a massive appetite, which is great if you're trying to bulk but also tends to make you incredibly tired. So there you go. Bunch of useless information. ---- If anyone is curious, this paper does an astounding job of summarizing the useful bits on Leptin + Ghrelin: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-789X.2006.00270.x https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-789X...

mrfusion 6y ago
Now why did the leptin diet pill never work out? Would injections work?
- gavinray 6y ago
  I would imagine the same persistent problem with human physiology -- which is the tendency towards homeostasis. Human body is remarkable in responsive to disturbances in balance. You can generally throw things off a fair degree before the systems behind whatever you've thrown off adapt and scale down responses. Generally when you see things in the extreme in humans, somewhere in the line there's a malfunction in regulation that allowed that state to be reached (or chemical intervention, e.g. anabolic steroids, substance abuse, etc). Almost anything will work for a little, but the only thing that works forever are things that can become lifestyle factors. There are a handful of exceptions for "magic diet pills", but please for the love of god don't listen to what I'm about to say below as anything more than science: - Phentermine - [Rx but can outright buy it from "Medical Spas" pretty cheap (how is this legal?)] Stimulatory appetitete suppressant, effects are essentially amphetamine minus the dopaminergic activity (no high, sorry) ---- - Sibutramine - [Rx, Phentermine's little brother] ---- - 2,4-Dinitrophenol (DNP) - [Not legal for sale, but you can buy it online if you're determined] It's what's called a "mitochondrial uncoupler". It disrupts the Krebbs Cycle so that resynthesis of ATP from ADP becomes incredibly inefficient, and it expels the discarded energy as heat. This is the holy grail of fatloss. You can lose 1.0-1.5lbs of pure adipose tissue (not water/glycogen) per day. But the excess heat will cause you an incurable, agonizing death if you overdose. Also makes you hot all day, probably dangerous if you work in the heat.
  - mrfusion 6y ago
    Interesting info. Thanks! I wonder if anyone has looked into DNP under medical supervision.
    - gavinray 6y ago
      DNP was one of the first anti-obesity medications, and was widely prescribed in the 1930s. It's use was discontinued, not actually due to overdose and death by heat, but because in some women it had a chance of causing cataracts, and if you're overly susceptible to oxidative stress/damage it can cause peripheral neuropathy. These effects are generally mitigated through supplementation efforts with anti-oxidants though.
      - piva00 6y ago
        What type of anti-oxidants would work? Vitamin C for example?

mrfusion 6y ago

Now why did the leptin diet pill never work out? Would injections work?

gavinray 6y ago
I would imagine the same persistent problem with human physiology -- which is the tendency towards homeostasis. Human body is remarkable in responsive to disturbances in balance. You can generally throw things off a fair degree before the systems behind whatever you've thrown off adapt and scale down responses. Generally when you see things in the extreme in humans, somewhere in the line there's a malfunction in regulation that allowed that state to be reached (or chemical intervention, e.g. anabolic steroids, substance abuse, etc). Almost anything will work for a little, but the only thing that works forever are things that can become lifestyle factors. There are a handful of exceptions for "magic diet pills", but please for the love of god don't listen to what I'm about to say below as anything more than science: - Phentermine - [Rx but can outright buy it from "Medical Spas" pretty cheap (how is this legal?)] Stimulatory appetitete suppressant, effects are essentially amphetamine minus the dopaminergic activity (no high, sorry) ---- - Sibutramine - [Rx, Phentermine's little brother] ---- - 2,4-Dinitrophenol (DNP) - [Not legal for sale, but you can buy it online if you're determined] It's what's called a "mitochondrial uncoupler". It disrupts the Krebbs Cycle so that resynthesis of ATP from ADP becomes incredibly inefficient, and it expels the discarded energy as heat. This is the holy grail of fatloss. You can lose 1.0-1.5lbs of pure adipose tissue (not water/glycogen) per day. But the excess heat will cause you an incurable, agonizing death if you overdose. Also makes you hot all day, probably dangerous if you work in the heat.
- mrfusion 6y ago
  Interesting info. Thanks! I wonder if anyone has looked into DNP under medical supervision.
  - gavinray 6y ago
    DNP was one of the first anti-obesity medications, and was widely prescribed in the 1930s. It's use was discontinued, not actually due to overdose and death by heat, but because in some women it had a chance of causing cataracts, and if you're overly susceptible to oxidative stress/damage it can cause peripheral neuropathy. These effects are generally mitigated through supplementation efforts with anti-oxidants though.
    - piva00 6y ago
      What type of anti-oxidants would work? Vitamin C for example?