What is GLP-1 & How Does It Reduce Appetite & Promote Weight Loss? | Dr. Andrew Huberman
What this covers
Dr. Andrew Huberman discusses how GLP-1, both the naturally occurring peptide and the newly popular GLP-1 drugs, work for appetite suppression and weight loss.
Full episode: https://youtu.be/m_OazsImOiI Show notes: https://hubermanlab.com/the-science-and-treatment-of-bipolar-disorder/
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A recent Cell paper reveals that appetite suppression operates through parallel neural and gut-based pathways working independently yet in concert, demonstrating a fundamental organizational principle of human biology that applies across many physiological systems.
- GLP-1 suppresses appetite through at least two independent mechanisms: gut distension via enteric neurons and direct brain hypothalamus activation via the gut-brain axis
- Parallel pathways are ubiquitous in biology, exemplified by dual epinephrine release from both adrenals and locus coeruleus during arousal
- Understanding this principle has practical implications for appetite management through both pharmaceutical GLP-1 drugs and natural compounds like yerba mate
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GLP-1 can stimulate mechanoreceptors of the gut through activation of intestinofugal enteric neurons, creating a sensation of fullness without actual physical food
“A peptide, not actual physical food, but a peptide that stimulates neurons that cause changes in the so-called mechanoreceptors of the gut, of the enteric nervous system, and make people feel full.”
GLP-1 suppresses appetite through at least two parallel mechanisms: by acting on intestinofugal enteric neurons to cause gut distension (making people feel full), and by stimulating the hypothalamus through the gut-brain axis to trigger satiety
“What this paper shows is that glucagon-like peptide one acts on receptors in the body in a portion of the nervous system called the enteric nervous system... GLP-1 binds to what are called intestinofugal enteric neurons. You don't need to know the name, but those neurons do two things. First of all, they cause some gut distension. So they actually make you feel full.”
The paper 'An inter-organ neural circuit for appetite suppression' published in Cell journal demonstrates that GLP-1 suppresses appetite through at least two independent parallel mechanisms: one via intestinofugal enteric neurons causing gut distension, and another via neural communication to the hypothalamus that triggers satiety.
“what this paper shows is it does that by at least two mechanisms through parallel pathways. What this paper shows is that glucagon-like peptide one acts on receptors in the body in a portion of the nervous system called the enteric nervous system”
The brain and body operate in concert through mechanisms that work independently in the brain and body but are directed toward common goals, often with bidirectional communication
“your brain and your body are acting in concert. They're acting together through mechanisms that either are independent, so separately in the brain and separately in the body but directed towards a common goal, or through communication between brain and body”
The principle of parallel pathways describes neural, hormonal, or other biological pathways that operate independently of one another to accomplish a common goal
“the principle of so-called parallel pathways. Parallel pathways, as the name suggests, are pathways that could be neural pathways or hormonal pathways or otherwise that operate independently of one another to accomplish a common goal”
Certain smoked varieties of yerba mate have potential carcinogenic effects, and the speaker actively avoids these forms of yerba mate despite otherwise using it regularly.
“Nonetheless, should also point out that yerba mate comes in a bunch of different forms. There is some concern about certain smokey flavored forms of yerba mate being carcinogenic, so that's why I avoid those forms of yerba mate”
Both epinephrine (adrenaline) release from the adrenal glands and epinephrine release from the locus coeruleus in the brain occur in parallel during states of positive or negative arousal (stress or excitement)
“there is a parallel activation of epinephrine, adrenaline, both from your adrenals and from an area in the brain called the locus coeruleus.”
Certain smokey-flavored forms of yerba mate have potential carcinogenic effects and should be avoided
“There is some concern about certain smokey flavored forms of yerba mate being carcinogenic, so that's why I avoid those forms of yerba mate”
Communication between the gut and brain through the enteric nervous system is bidirectional, with signals traveling from gut to brain and from brain to gut
“These enteric neurons are communicating to the brain, the hypothalamus, by way of this what's called the sympatho-gastro-spinal-reticular-hypothalamic pathway.”
GLP-1 acts on intestinofugal enteric neurons in the enteric nervous system, which are part of the autonomic nervous system that operates without conscious control.
“glucagon-like peptide one acts on receptors in the body in a portion of the nervous system called the enteric nervous system, e-n-t-e-r-i-c, enteric nervous system. This is a component of your nervous system that you don't really have control over. It's autonomic or automatic. GLP-1 binds to what are called intestinofugal enteric neurons.”
When people are excited by something (whether positive or negative/stressful), there is a parallel activation of epinephrine (adrenaline) from both the adrenal glands and from the locus coeruleus in the brain, illustrating the parallel pathway principle.
“Another good example of this would be when we are excited by something positive or negative, so it could be stressful or we're positively aroused, there is a parallel activation of epinephrine, adrenaline, both from your adrenals and from an area in the brain called the locus coeruleus.”
When GLP-1 binds to intestinofugal enteric neurons, it causes gut distension by stimulating mechanoreceptors of the enteric nervous system, creating a sensation of fullness without actual physical food being present.
“those neurons do two things. First of all, they cause some gut distension. So they actually make you feel full. This is incredible, right? A peptide, not actual physical food, but a peptide that stimulates neurons that cause changes in the so-called mechanoreceptors of the gut, of the enteric nervous system, and make people feel full.”
GLP-1 suppresses appetite through a second mechanism by which intestinofugal enteric neurons communicate to the hypothalamus via the sympatho-gastro-spinal-reticular-hypothalamic pathway, activating neural pathways that trigger satiety (the feeling of having had enough food).
“by way of a pathway that goes from the gut up to the hypothalamus, this little cluster of neurons about the size of a marble that sits above the roof of your mouth is also suppressing appetite through brain mechanisms. So this is really beautiful, right? You have a peptide, a small little protein, that's released in the gut and that release within the gut causes gut distension which makes you feel full, and by way of neural stimulation of the hypothalamus also activates neural pathways within the brain that trigger satiety, the feeling of having had enough food.”
GLP-1 (glucagon-like peptide one) is a peptide that can dramatically suppress appetite and is the basis for new prescription drugs showing impressive clinical trial results for type 2 diabetes and obesity treatment.
“It is a peptide, which is a small little protein, that can dramatically suppress appetite. So that's why these drugs are being explored and are showing quite impressive results for things like treatment of type two diabetes and other forms of diabetes, as well as obesity.”
GLP-1 (glucagon-like peptide one) is a peptide that can dramatically suppress appetite and is the target of new prescription drugs showing impressive clinical results for type 2 diabetes and obesity treatment
“It is a peptide, which is a small little protein, that can dramatically suppress appetite. So that's why these drugs are being explored and are showing quite impressive results for things like treatment of type two diabetes and other forms of diabetes, as well as obesity”
Parallel pathways are neural or hormonal pathways that operate independently of one another to accomplish a common goal, and this is a fundamental principle of biological organization.
“Parallel pathways, as the name suggests, are pathways that could be neural pathways or hormonal pathways or otherwise that operate independently of one another to accomplish a common goal.”
The brain and body act in concert through mechanisms that are either independent (operating separately in the brain and separately in the body but directed toward a common goal) or through bidirectional communication (body-to-brain and brain-to-body).
“your brain and your body are acting in concert. They're acting together through mechanisms that either are independent, so separately in the brain and separately in the body but directed towards a common goal, or through communication between brain and body, and almost always that communication is going to be bidirectional. Body to brain and brain to body.”
New prescription drugs that stimulate GLP-1 or are synthetic versions of GLP-1 are hitting the market and showing impressive clinical results for diabetes and obesity
“there are also new prescription drugs that are now hitting the market and for which there are really impressive clinical trials for diabetes and obesity that are essentially glucagon-like peptide one stimulators, so they stimulate the release of that, or they are in fact a synthetic version of glucagon-like peptide one.”
The amount of GLP-1 released from drinking yerba mate is much lower than the amount released by GLP-1-stimulating drugs or synthetic GLP-1 drugs.
“Now in terms of the yerba mate stimulation of glucagon-like peptide one, that's going to be a much lower amount of glucagon-like peptide one that's released from drinking yerba mate as opposed to, say, taking a drug that stimulates GLP-1 or taking a drug that is GLP-1.”
GLP-1-based drugs that stimulate the release of GLP-1 or deliver synthetic GLP-1 lead to weight loss.
“So they lead to weight loss.”
The amount of GLP-1 released from drinking yerba mate is much lower than the amount released or provided by GLP-1-stimulating drugs or synthetic GLP-1 drugs
“in terms of the yerba mate stimulation of glucagon-like peptide one, that's going to be a much lower amount of glucagon-like peptide one that's released from drinking yerba mate as opposed to, say, taking a drug that stimulates GLP-1 or taking a drug that is GLP-1”
Understanding the parallel pathway principle is important not just for weight loss and appetite suppression, but generally for understanding how biological systems are organized at a fundamental level.
“And then for everybody, not just those that are interested in appetite suppression, I think it's important to understand that these parallel pathways are fundamental to how we are organized.”
The level of GLP-1 stimulation from drinking yerba mate is expected to cause mild gut distension that produces mild appetite suppression, whereas very high levels (as from synthetic drugs) would cause major gut distension that would be uncomfortable.
“Okay, I think that the levels of GLP-1 that would come from drinking yerba mate and hopefully from appropriate dosaging of the synthetic forms of GLP-1 or drugs that stimulate GLP-1 would cause mild, not major gut distension, 'cause major gut distension would be uncomfortable.”
For people looking for mild appetite suppression while also ingesting caffeine, yerba mate is a good option because it stimulates GLP-1 release and provides both mild gut distension effects and brain-level satiety effects.
“things like yerba mate and I'm sure there are other compounds out there as well, but certainly yerba mate can stimulate the release of GLP-1, so for those of you that are looking for some mild appetite suppression and want to accomplish that while also ingesting caffeine, yerba mate might be a good option for that, and just know that it's operating through two mechanisms on the body through mild gut distension to make you feel full and on the brain to increase satiety or make you feel less hungry.”
Yerba mate is a tea that promotes the release of glucagon-like peptide one and is a preferred source of caffeine for the speaker
“I'm a big proponent and consumer of yerba mate. Yerba mate is a tea that can promote the release of glucagon-like peptide one”
Understanding the parallel pathways principle is important not only for weight loss and appetite suppression but for understanding how humans are organized at a biological level
“I think these results are really interesting and really important for sake of weight loss, for sake of appetite suppression, and just generally for the way that they illustrate this very important theme of the way that we are constructed at a biologic level, which is parallel pathways.”
Yerba mate is a tea that promotes the release of glucagon-like peptide one and is one of the speaker's preferred sources of caffeine for early-day focus and work.
“I'm a big proponent and consumer of yerba mate. Yerba mate is a tea that can promote the release of glucagon-like peptide one”
The speaker considers GLP-1 'impressive and important' because recent drugs based on GLP-1 can help adjust obesity and weight loss through at least two independent mechanisms: one in the brain and one in the gut with communication via the gut-brain axis.
“So to me, GLP-1 is both impressive and important. Why? Because this recent category of drugs that's now hitting the market seems to adjust obesity or can help people with weight loss in order to help their health, and it's doing so by at least two mechanisms. One is within the brain and the other is within the gut and communication through the so-called gut brain access.”
Appropriate dosing of synthetic GLP-1 or GLP-1-stimulating drugs would cause mild gut distension, whereas very high levels could cause major, uncomfortable distension
“I think that the levels of GLP-1 that would come from drinking yerba mate and hopefully from appropriate dosaging of the synthetic forms of GLP-1 or drugs that stimulate GLP-1 would cause mild, not major gut distension, 'cause major gut distension would be uncomfortable.”
The speaker is a consumer of yerba mate and highlights both its benefits (GLP-1 release, caffeine for focus and exercise) and its risks (carcinogenic compounds in smokey varieties)
“I'm a big proponent and consumer of yerba mate... for me, yerba mate is one of the preferred sources of caffeine for me, I like the way it tastes. It does provide the sort of caffeine kick that I like to have early in the day for focus and for work and for exercise, and yet I actively avoid the smoked varieties of yerba mate because of the potential carcinogenic effects of the smoked varieties.”
The enteric nervous system is a component of the nervous system that operates autonomously and is not under conscious control
“This is a component of your nervous system that you don't really have control over. It's autonomic or automatic.”
The hypothalamus is a small cluster of neurons approximately the size of a marble located above the roof of the mouth and plays a role in appetite suppression
“by way of a pathway that goes from the gut up to the hypothalamus, this little cluster of neurons about the size of a marble that sits above the roof of your mouth”
The paper is entitled 'An inter-organ neural circuit for appetite suppression'.
“this paper entitled 'An inter-organ neural circuit for appetite suppression'”
The hypothalamus is a small cluster of neurons approximately the size of a marble that sits above the roof of the mouth and plays a central role in appetite regulation.
“by way of a pathway that goes from the gut up to the hypothalamus, this little cluster of neurons about the size of a marble that sits above the roof of your mouth”
Cell is described as 'a Cell Press journal' and is one of the three apex journals of scientific publishing.
“This is a paper published in the journal, 'Cell,' which is a Cell Press journal, an excellent journal, in fact, one of the three apex journals.”
Yerba mate is available in multiple different forms, some of which differ in their potential health effects.
“Nonetheless, should also point out that yerba mate comes in a bunch of different forms.”
Papers published in Nature, Science, and Cell are considered the apex journals in their respective fields, analogous to the Super Bowl, Stanley Cup, and NBA championships of publishing
“papers published in the journal, 'Nature,' 'Science,' and 'Cell' are considered the sort of Super Bowl, Stanley Cup, and NBA championships of publishing”
Papers published in Nature, Science, and Cell are considered the apex journals ('the Super Bowl, Stanley Cup, and NBA championships' of academic publishing).
“papers published in the journal, 'Nature,' 'Science,' and 'Cell' are considered the sort of Super Bowl, Stanley Cup, and NBA championships of publishing.”