What is GLP-1 & How Does It Reduce Appetite & Promote Weight Loss? | Dr. Andrew Huberman
00:00:00.000 | I want to highlight some recent findings in an area totally
00:00:05.000 | separate from mental health that I think are really
00:00:09.320 | important for everyone to know about.
00:00:10.940 | This is a paper published in the journal Cell,
00:00:12.960 | which is a Cell Press journal, an excellent journal.
00:00:15.040 | In fact, one of the three apex journals.
00:00:16.880 | So for those of you that are curious,
00:00:18.440 | papers published in the journal Nature, Science, and Cell
00:00:21.560 | are considered the sort of Superbowl, Stanley Cup,
00:00:25.040 | and NBA championships of publishing.
00:00:27.180 | And this paper entitled an Interorgan Neural Circuit
00:00:31.040 | for Appetite Suppression,
00:00:32.360 | illustrates a very important principle
00:00:34.140 | that I think everyone should know about.
00:00:35.800 | And that's the principle of so-called parallel pathways.
00:00:39.200 | Parallel pathways, as the name suggests,
00:00:41.640 | are pathways that could be neural pathways
00:00:43.680 | or hormonal pathways or otherwise,
00:00:46.700 | that operate independently of one another
00:00:49.180 | to accomplish a common goal.
00:00:51.800 | And what this paper really shows
00:00:53.520 | is that there's a set of peptides in the body.
00:00:57.380 | And the peptide that I'm referring to today
00:00:59.460 | is called a GLP-1, glucagon-like peptide one,
00:01:03.220 | and some related peptides.
00:01:04.480 | I've talked about these on the podcast before
00:01:06.720 | for two reasons.
00:01:07.540 | First of all, I'm a big proponent and consumer of yerba mate.
00:01:12.540 | Yerba mate is a tea that can promote the release
00:01:15.400 | of glucagon-like peptide one.
00:01:17.740 | And there are also new prescription drugs
00:01:20.400 | that are now hitting the market,
00:01:21.720 | and for which there are really impressive clinical trials
00:01:23.800 | for diabetes and obesity,
00:01:25.720 | that are essentially glucagon-like peptide one stimulator.
00:01:29.960 | So they stimulate the release of that,
00:01:31.200 | or they are in fact a synthetic version
00:01:34.040 | of glucagon-like peptide one.
00:01:35.680 | What is glucagon-like peptide one?
00:01:37.880 | It is a peptide, which is a small little protein
00:01:40.720 | that can dramatically suppress appetite.
00:01:43.880 | So that's why these drugs are being explored
00:01:46.240 | and are showing quite impressive results
00:01:49.080 | for things like treatment of type two diabetes
00:01:51.980 | and other forms of diabetes, as well as obesity.
00:01:55.280 | So they lead to weight loss.
00:01:56.800 | Now, in terms of the yerba mate stimulation
00:01:58.740 | of glucagon-like peptide one,
00:02:00.040 | that's going to be a much lower amount
00:02:01.960 | of glucagon-like peptide one that's released
00:02:03.820 | from drinking yerba mate,
00:02:05.400 | as opposed to say, taking a drug that stimulates GLP-1
00:02:08.880 | or taking a drug that is GLP-1.
00:02:11.300 | Nonetheless, I should also point out
00:02:14.040 | that yerba mate comes in a bunch of different forms.
00:02:17.380 | There is some concern about certain smoky flavored forms
00:02:21.820 | of yerba mate being carcinogenic.
00:02:24.060 | So that's why I avoid those forms of yerba mate.
00:02:26.580 | But for me, yerba mate is one of the preferred sources
00:02:28.940 | of caffeine for me.
00:02:30.060 | I like the way it tastes.
00:02:31.260 | It does provide that sort of caffeine kick
00:02:33.200 | that I like to have early in the day for focus
00:02:34.980 | and for work and for exercise.
00:02:36.980 | And yet I actively avoid the smoked varieties
00:02:39.700 | of yerba mate because of the potential carcinogenic effects
00:02:42.820 | of the smoked varieties.
00:02:45.060 | Glucagon-like peptide one, as I mentioned earlier,
00:02:47.780 | can suppress appetite.
00:02:49.520 | But what this paper shows is it does that
00:02:52.700 | by at least two mechanisms through parallel pathways.
00:02:56.460 | What this paper shows is that glucagon-like peptide one
00:03:00.100 | acts on receptors in the body,
00:03:01.940 | in a portion of the nervous system
00:03:03.380 | called the enteric nervous system,
00:03:05.300 | E-N-T-E-R-I-C, enteric nervous system.
00:03:08.740 | This is a component of your nervous system
00:03:10.020 | that you don't really have control over.
00:03:11.600 | It's autonomic or automatic.
00:03:13.980 | GLP-1 binds to what are called
00:03:16.020 | intestinal fugal enteric neurons.
00:03:18.600 | You don't need to know the name,
00:03:19.780 | but those neurons do two things.
00:03:21.480 | First of all, they cause some gut distention.
00:03:24.980 | So they actually make you feel full.
00:03:27.140 | This is incredible, right?
00:03:28.260 | A peptide, not actual physical food,
00:03:30.620 | but a peptide that stimulates neurons
00:03:34.020 | that cause changes in the so-called mechanoreceptors
00:03:37.160 | of the gut of the enteric nervous system
00:03:39.620 | and make people feel full.
00:03:41.340 | So it can lead to actually mild,
00:03:43.320 | or I suppose, if levels of GLP-1 are very high,
00:03:45.880 | to major gut distention, okay?
00:03:48.140 | I think that the levels of GLP-1
00:03:49.780 | that would come from drinking yerba mate
00:03:51.220 | and hopefully from appropriate dosaging
00:03:53.240 | of the synthetic forms of GLP-1
00:03:56.340 | or drugs that stimulate GLP-1
00:03:57.700 | would cause mild, not major gut distention,
00:04:00.020 | 'cause major gut distention would be uncomfortable.
00:04:02.460 | So GLP-1 is acting at the level of gut
00:04:04.820 | to increase gut distention and by way of a pathway
00:04:09.220 | that goes from the gut up to the hypothalamus,
00:04:11.640 | this little cluster of neurons about the size of a marble
00:04:14.260 | that sits above the roof of your mouth,
00:04:15.820 | is also suppressing appetite through brain mechanisms.
00:04:19.340 | So this is really beautiful, right?
00:04:20.740 | You have a peptide, a small little protein
00:04:22.900 | that's released in the gut,
00:04:24.820 | and that release within the gut causes gut distention,
00:04:29.300 | which makes you feel full,
00:04:30.480 | and by way of neural stimulation of the hypothalamus
00:04:33.540 | also activates neural pathways within the brain
00:04:36.100 | that trigger satiety, the feeling of having had enough food.
00:04:39.420 | So to me, GLP-1 is both impressive and important.
00:04:42.560 | Why?
00:04:43.400 | Because this recent category of drugs
00:04:45.560 | that's now hitting the market seems to adjust obesity
00:04:49.460 | or can help people with weight loss
00:04:50.840 | in order to help their health.
00:04:52.560 | And it's doing so by at least two mechanisms.
00:04:55.160 | One is within the brain
00:04:56.240 | and the other is within the gut and communication
00:04:59.200 | through the so-called gut-brain axis.
00:05:01.400 | Because again, these enteric neurons
00:05:03.160 | are communicating to the brain, the hypothalamus,
00:05:06.160 | by way of this, what's called
00:05:07.620 | the sympathogastro-spinal reticular hypothalamic pathway.
00:05:11.380 | You absolutely do not need to know all of that.
00:05:13.500 | That's a mouthful.
00:05:14.340 | That's enough to make your mouth feel distended.
00:05:16.300 | But at the same time, things like yerba mate,
00:05:19.300 | and I'm sure there are other compounds out there as well,
00:05:21.120 | but certainly yerba mate can stimulate the release of GLP-1.
00:05:24.180 | So for those of you that are looking
00:05:25.300 | for some mild appetite suppression
00:05:27.180 | and want to accomplish that while also ingesting caffeine,
00:05:30.220 | yerba mate might be a good option for that.
00:05:32.180 | And just know that it's operating through two mechanisms,
00:05:35.020 | on the body through mild gut distension
00:05:36.820 | to make you feel full and on the brain
00:05:38.280 | to increase satiety or make you feel less hungry.
00:05:41.040 | And then for everybody,
00:05:42.560 | not just those that are interested in appetite suppression,
00:05:45.200 | I think it's important to understand
00:05:47.220 | that these parallel pathways are fundamental
00:05:49.440 | to how we are organized.
00:05:50.920 | Another good example of this would be
00:05:52.280 | when we are excited by something, positive or negative,
00:05:54.760 | so it could be stressful or we're positively aroused,
00:05:57.320 | there is a parallel activation of epinephrine, adrenaline,
00:06:00.640 | both from your adrenals
00:06:01.800 | and from an area in the brain called the locus coeruleus.
00:06:04.240 | So again and again,
00:06:05.340 | we see this in biology and in neuroscience,
00:06:07.800 | that your brain and your body are acting in concert,
00:06:10.880 | they're acting together through mechanisms
00:06:13.200 | that either are independent,
00:06:14.640 | so separately in the brain and separately in the body,
00:06:16.920 | but directed towards a common goal
00:06:19.420 | or through communication between brain and body.
00:06:21.920 | And almost always that communication
00:06:24.080 | is going to be bi-directional,
00:06:25.400 | body to brain and brain to body.
00:06:27.360 | So I think these results are really interesting
00:06:29.200 | and really important for sake of weight loss,
00:06:31.200 | for sake of appetite suppression,
00:06:33.160 | and just generally for the way that they illustrate
00:06:35.560 | this very important theme
00:06:37.200 | of the way that we are constructed at a biological level,
00:06:40.040 | which is parallel pathways.
00:06:42.180 | [upbeat music]
00:06:45.460 | [upbeat music]
00:06:48.040 | (upbeat music)