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BEN BIKMAN | BEIGE FAT …subcutaneous fat can be beiged…burns 3X faster… — Transcript

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0:00Now as we start talking about fat, let's
0:02firstly explore why we store fat.
0:06Because it is something that we don't
0:08take to very warmly. Unfortunately, we
0:11curse what we pinch and jiggle when in
0:14reality we should be quite grateful for
0:16it. First and foremost is the most
0:19obvious benefit of having fat, which is
0:21it allows us to survive a time of
0:24nutrient deficiency or caloric
0:25deficiency.
0:27Now in this day and age that seems like
0:30it's something very silly. The idea of
0:34having insufficient access to food is
0:37almost laughable for for most of us. Now
0:41however um it doesn't take a lot to
0:43imagine a scenario where things could
0:44change quite quickly due to employment
0:47circumstances or economic or societal
0:49problems. Should such u disasters ever
0:53happen, we would be very grateful for
0:54our fat. It allows us to fast is one way
0:58of describing it. So it allows us to
1:01survive any period of scarcity
1:03whatsoever.
1:05So that's important. Now another thing
1:07about why we store fat is that's worth
1:10highlighting is the uniqueness of
1:11humans. Now humans are unique on this
1:14planet in a number of ways. In a number
1:18of ways. Myriad
1:20things differentiate us from every other
1:22animal on the planet. Among them is our
1:26metabolic capacity. That humans in
1:30particular, we are the only landbased
1:33mammals that are obese. And we're
1:36certainly the only ones that are born
1:37obese. Now, there are some other animals
1:39that can get fat, but even animals that
1:42you typically think of as fat aren't
1:44really like a cow. A cow is very, very
1:47lean. You think of other primates, even
1:51a lean human coming in at, let's say, 8%
1:54body fat would be considered obese if we
1:56compared that human to say apes or
1:59orangutans. Now, those animals may have
2:02really distended bellies, but it's just
2:04because they're fermenting so much of
2:05the plants they're eating that it's
2:07constantly distended. But in reality,
2:10the actual amount of body fat they have
2:12is exquisitly low. So, we are again very
2:15unique in that we are born obese. We are
2:17the only mammals land-based because u
2:20water-based like dolphins or whales of
2:22course are a bit of an exception.
2:24They're fatter, but we're not them. We
2:27don't live on the ocean. We don't we
2:28live on the land and we're the only ones
2:30born obese. Now, why? That's a matter of
2:34some speculation,
2:35um some theory when it comes to some of
2:37the understandings of how we became who
2:40we are. How did we become the thinking
2:43bigrained humans that we are today?
2:45There is there is a theory in the realm
2:48of evolution as it's all theoretical um
2:52that is called the expensive tissue
2:54hypothesis and the expensive tissue
2:57hypothesis
2:59uh posits that we and there's another
3:01theory I'll mention in a moment that's a
3:03little more closely related but the
3:04expensive tissue hypothesis basically
3:06posits that it's our ability to both eat
3:09and store more fat that allowed our
3:12brains to get bigger and our intestines
3:15to get shorter and those are some of the
3:17substantial differences between humans
3:20and other primates like apes etc. Now
3:23the another theory of evolution is one
3:26called the shorebased theory of
3:27evolution and that is a little more
3:30nuanced but this most succinct version
3:32of it is perhaps that we are born um
3:36with large brains and the shore-based
3:38theory being that we have access to
3:41omega-3 fats in particular that help
3:44fuel brain growth. But then as a part of
3:47that theory is this idea that by being
3:50born obese a baby has the ability to
3:53born a human baby has the ability to
3:55born to to burn a lot of fat and when we
3:59burn a lot of fat we make ketones very
4:02very readily.
4:04Now there are some funny ideas about
4:07ketones burning a baby's brain or some
4:10such nonsense. The reality of human
4:13metabolism is that when a human baby
4:15doesn't eat for just a couple hours,
4:17they will get into a deep they're
4:19burning so much fat because they have so
4:21much fat because they're born obese that
4:23they will get into a deeper state of
4:25ketosis than an adult human will after
4:28even about two hour two days rather
4:30straight of fasting. So babies get into
4:33deep ketosis substantially and very very
4:36quickly and it's thought to be uh an
4:40adaptive mechanism to help fuel the
4:42brain because the brain thrives so well
4:43on ketone. But it is worth appreciating
4:47that perhaps one of the reasons we are
4:50born fat is because our brain benefits
4:53so much from that fat because of our
4:55ability to rely on fat as a primary
4:57metabolic fuel and in so doing creating
5:01ketones to fuel the brain because the
5:03more we're learning about brain
5:05metabolism and here I am coming back to
5:06that topic the more we appreciate that
5:09the brain thrives on ketones. Now, in
5:13addition to the caloric reserve and the
5:17potential to protect ourselves from
5:19scarcity with [snorts] fat and the
5:21energy that it stores
5:24is just the fact that fat can provide
5:26some degree of protection and insulation
5:30um insulation, particularly as fat is
5:33stored beneath the skin, which we'll get
5:34to in a moment, but also a protection as
5:38fat is stored within the visceral space.
5:41the fat that is stored deeper within the
5:43abdominal cavity. It provides a
5:46structure or shape to the intestines and
5:48even some degree of indeed a protection.
5:51It's also very much a part of the immune
5:53system. Speaking of the visceral fat,
5:56that is the fat again that's deep within
5:57the abdominal cavity. It is richly
6:01loaded with lymph nodes. lymph nodes of
6:04course being a primary component or in
6:07fact tech if I'm being technical a
6:09secondary component of of the immune
6:11system where we can take immunereated
6:14cells and let them kind of incubate and
6:16get primed for action and then go fight
6:19an infection. So visceral fat is very
6:22much connected to the immune system and
6:24that ends up actually being a blessing
6:26and a curse as we'll get to later. Okay,
6:29now let's transition from the
6:30evolutionary role and some of the
6:32theories of why we are uniquely fat
6:34among the mammals on on the earth
6:38and then let's move into understanding
6:40the different types of fat.
6:43Now, [clears throat] there are two
6:44different ways of classifying fat tissue
6:47and you've heard these before, I'm sure.
6:50One way is where we store it and then
6:52the other way is how that fat behaves.
6:56So, let's just talk about the actual
6:57location because it's the simplest idea.
7:00We primarily store fat in two depots,
7:04two distinct areas, and that is
7:06subcutaneous. That's the fat that's
7:08stored right beneath the skin that I
7:10just mentioned a moment ago that acts as
7:11a bit of an insulation. So, we have
7:13subcutaneous fat and then we have
7:15visceral fat. Again, both of these are
7:17fats I just mentioned. Visceral fat
7:19being the fat that is stored deeper
7:20within the abdominal cavity. Now, there
7:23are some sex um differences and um
7:26genetics that play into this that we'll
7:27get to in a moment. But one way of
7:30thinking about the differences is if you
7:33can pinch and jiggle it, it is
7:36subcutaneous fat.
7:39Um and then visceral fat of course is
7:41fat you cannot see. However, let's
7:44imagine if you will two men. They are
7:47best pals. They do everything together
7:49and they've both gained 50 pounds of
7:51pure fat since they graduated from
7:53college 30 years ago. Not an uncommon
7:55amount of fat gain.
7:58They've gained the same amount of body
7:59fat again. Then they're the same weight,
8:01same height, everything. But you look at
8:03them and one of them has fat that is
8:06spilling over his swim trunks. It's just
8:09sort of gushing or or kind of flowing
8:11down his body, hanging on him. The other
8:14man, you can pinch and jiggle. And boy,
8:16does it jiggle. The other guy has a big
8:19protruding belly and it does not jiggle
8:22it. It you smack it and it is hard.
8:25Which one of those two fellas do you
8:27think has more subcutaneous fat or in
8:30other words fat that is stored beneath
8:31the skin? And which one do you think has
8:34more visceral fat? Fat stored within the
8:36abdominal cavity. Yeah, of course the
8:38subcutaneous fat is the former, the one
8:41whose fat is pinchable and jiggable and
8:43spilling down over the sides of his swim
8:45trunks. And the other fellow who looks
8:47like he's carrying a baby is in fact
8:50just carrying a lot of visceral fat. And
8:53that visceral fat is accumulating
8:54beneath the muscles of his abdomen. And
8:58so when you smack it, it is hard because
9:01you're smacking his skin and muscle and
9:03then the fat is beneath that. If we
9:06store fat through hyperplasia,
9:08which is the production or
9:10multiplication of fat cells, then the
9:13fat cells are smaller. Even if they are
9:15more abundant, they are smaller. And
9:18smaller fat cells are insulin sensitive
9:20and healthy. They're anti-inflammatory
9:23fat cells as well. In contrast, if we
9:27are storing fat through hypertrophy,
9:30that is when fat cells are all getting
9:32bigger individually. The number of fat
9:34cells isn't changing, but the size is
9:36changing.
9:38And those fat cells become insulin
9:40resistant and pro-inflammatory for
9:42reasons we've discussed previously.
9:46Subcutaneous fat tends to be stored as
9:49hyperlastic fat. So they're smaller,
9:51more abundant fat cells. And then
9:54visceral fat tends to be stored more as
9:58hyper hypertrophic fat cells. So fewer
10:01in number but larger in size. Now as I
10:04mentioned there's another way of
10:05classifying fat as we understand the
10:07different types of fat and that is
10:09looking at its metabolic behavior.
10:12Normally when we think of fat tissue
10:14you're think you would imagine a tissue
10:17or cells uh that have a very low
10:19metabolic rate and you would be right.
10:22In fact, as a scientist who has done
10:24these studies, I can assure you that fat
10:27cells do in fact have a metabolic rate
10:29that is so low that it is almost below
10:31the point of detection. That when we're
10:34testing metabolic rate in fat tissue, it
10:36is just you have to really zoom in to
10:39see any of the actual metabolic rate of
10:42those cells.
10:44Now, there's that is what we would call
10:47white fat. And that fat does look quite
10:51white. It looks like Crisco or coconut
10:54oil. It really is. I mean, not quite as
10:57bright white as those, but it is very,
10:59very white. Um, and that is reflective
11:02of just the pure amount of fat that is
11:05being stored within those fat cells. You
11:08see practically nothing else. And in
11:10fact, if you look at fat cells under a
11:12microscope, all you see is this big
11:15round blob. Normally if you look at like
11:18if we were to look at muscle cells it's
11:20a very busy thing. It's very dark
11:22pigmented because you're getting the
11:25nucleus lots of mitochondria lots of
11:27endopplasmic reticulum and all and
11:30losomes and all kinds of other parts of
11:32the cell. But within the fat cell all of
11:35that has been the fat cell has all of
11:37those things but all of it's been pushed
11:39to the edges to because it's this big
11:42bubble of fat is filling up the fat
11:45cell. It is something called the lipid
11:47droplet and it is one big fat lipid
11:51droplet and everything else has been
11:53pushed to up to the very edges the
11:55nucleus the mitochondria and all the
11:57other organels and pieces of the cells I
11:59just mentioned. So you only see this big
12:02blob of fat. That is white fat. And
12:05again, it has a very, very low metabolic
12:07rate that stands in stark contrast,
12:11functionally speaking, and in
12:13appearance, to what we commonly call
12:15brown fat. Brown fat, as you might
12:18imagine, looks quite brown. In fact,
12:20it's kind of a reddish brownish hue. And
12:23that's reflective, in fact, of a much
12:25higher density of mitochondria in part.
12:29So there's a much higher amount of
12:31mitochondria which do tend to stain or
12:33reflect a bit of a ruddy brownish
12:35appearance. But if you look within the
12:38brown fat cells,
12:40you don't have one big blob of fat or
12:43one massive lipid droplet to use the
12:45technical term. You have countless small
12:48little lipid droplets. Now that's an
12:51advantage metabolically for a cell that
12:53wants to burn fat. If you have a lot of
12:56smaller
12:58um lipid droplets, you have a much more
12:59surface area where you can come in and
13:01start pulling the fat off of it to burn.
13:04And that is what the brown fat wants to
13:06do with all of those mitochondria.
13:09The fat, the brown fat cells want to
13:12burn energy. And burn is the appropriate
13:14verb to use here because it also evokes
13:17the sense of heat. And that's what it
13:19wants to do. It's not burning the fat or
13:22glucose in order to get work done like
13:24say a muscle cell would do. A muscle
13:27cell is burning calories because it
13:29wants to work. It wants to contract and
13:31relax. Well, a fat cell has no such job.
13:34It is in fact kind of inert. It's lazy.
13:36It's just sitting there. But brown fat
13:39is burning that energy to create heat.
13:42And one interesting difference, we're
13:44going to talk more about age next time,
13:46but one interesting difference when you
13:48compare babies to adults within the
13:50human family, babies have much more
13:53brown fat. And this is probably an
13:56adaptive mechanism because a newborn
13:58baby also has very little muscle. And so
14:01if baby gets cold, baby doesn't really
14:04have a good way to warm up. An adult
14:06does, an adult can shiver. And as the
14:08muscles start twitching, they start
14:10generating heat from those biochemical
14:12reactions. But a baby can't shiver. And
14:15so the baby has much more brown fat
14:18which enables baby to be warm without
14:20the need for shivering.
14:24And that feature of brown fat tissue
14:27happens not only because of the much
14:29higher amount of mitochondria, but also
14:32the higher expression of a very
14:34interesting protein called uncoupling
14:36protein one. We have these two overall
14:39types. Now, there's actually one that
14:41slips in between between white fat and
14:43brown fat. And just as a final note on
14:45brown fat, while white fat has a
14:47metabolic rate that is so low it's hard
14:49to detect. As a scientist, we've
14:51published those reports. Brown fat
14:53actually has a metabolic rate that is on
14:56par with what we see in skeletal muscle.
14:59Now muscle has a pretty decent metabolic
15:02rate and brown fat does too. It is
15:04multiple times high like an order of
15:06magnitude 10 times higher than what you
15:08see from white fat. Now again in between
15:11the two is something that is commonly
15:14called beige fat. And we even as
15:17scientists create this weird verb where
15:20you can take white fat and beige it or
15:24the white fat cells have undergone
15:26Beijing. So you can see how we're making
15:28this verb, this action of this process
15:31of taking the very low metabolic rate,
15:35low mitochondrial density white fat and
15:38having it start to behave kind of like
15:40brown fat. Now white fat is the fat that
15:44we're storing on our bodies. it to a
15:46large degree. All subcutaneous fat, the
15:49pinchable jigable is all white fat.
15:51Visceral fat, the deeper abdominal
15:53cavity fat is all white fat. Now, what
15:56we have found and others have found as
15:58well, we've published reports from
15:59animals and humans, you can you have a
16:02potential in the white fat to undergo a
16:05modest degree of Beijing. So, it starts
16:08to increase its mitochondrial density
16:10and some uncoupling. And we found that
16:12humans can increase their fat tissue
16:15metabolic rate from their subcutaneous
16:16fat by up to about three times simply by
16:20in fact by being in ketosis actually.
16:23And we hope to do some more studies to
16:24try to optimize the timing of all of
16:26that and find out how quickly it can
16:28happen. But suffice it to say uh it is
16:32white fat at the subcutaneous
16:35depot is capable of undergoing this
16:37modest conversion to behave a little
16:39more like brown fat. There's no evidence
16:41to suggest that visceral fat can do
16:44that. Indeed, in our studies of animals,
16:46we did not do visceral atapose biopsies
16:48in humans. That would be very difficult
16:50to do. Um, but in animals, we saw that
16:53the visceral fat did not experience this
16:55change like the subcutaneous fat did. So
16:58this is another reason why subcutaneous
17:01[clears throat]
17:02fat appears to be a little more
17:04beneficial, a little more favorable than
17:06visceral. Not only because of its
17:08potential for a little more hyperplasia,
17:10allowing the fat cells to stay smaller,
17:12but also this potential for the fat
17:14cells to get a little hotter, if you
17:16will, to have a little more mitochondria
17:18and uncoupling.
17:20First of all, it's just worth
17:21highlighting the digestion of nutrients.
17:24That when we eat fat, that fat will move
17:28through it gets digested in a bit of a
17:30curious way, which is that unlike any of
17:32the other nutrients, it moves into the
17:34lymph first and then after moving
17:37through the lymph, it comes into the
17:39blood vessels where it can then start
17:41interacting with cells and getting
17:42stored. And it is doing so on a
17:45kyomicron
17:46and it's moving within that big
17:48kyomicron like a big bus. It's being
17:51carried in the form of if of
17:53triglycerides
17:54and then different tissues are going to
17:57pull a little bit from that but
17:58generally the kyomicron is going to go
18:00to the liver and the liver is going to
18:01take care of it. It's going to store
18:03some or it's going to repackage it and
18:04release it as a VLDL another bus that's
18:08carrying different fats and different
18:10proteins.
18:11So that's a little bit of the digestion
18:13process. But if we come to the level of
18:15the fat cell because after all this is a
18:17conversation about storing fat
18:21you the fat cell will store fat from
18:23both fat
18:26circulating in the blood from
18:28triglyceride from triglyceride rich
18:30lipoproteins to be very precise that is
18:32generally VLDL and LDL a little bit of
18:35kyomicron but again generally the
18:36kyomicron from the diet just goes to the
18:38liver and then liver will decide what to
18:40do with it including dumping out some or
18:43a And that's going to be VLDLDL and LDL.
18:45So those are all the triglyceride rich
18:47lipoproteins that if they float past a
18:50fat cell, the fat cell has on its
18:53surface and other cells do too an enzyme
18:56called lipoprotein lipase. And this is
18:59an important little thing I'm going to
19:00tell you, which is where you have
19:03lipoprotein lipase determines where you
19:06store fat. Not necessarily how much fat
19:10you store, but where you store fat.
19:12You'll notice that you don't store fat
19:14everywhere on your body. For example, I
19:16don't store fat on the top of my head.
19:18It'd be nice to have something there,
19:19but I don't store fat there. You don't
19:21either. I don't store fat on the back of
19:22my hand or anywhere on my hand. I don't
19:25have lipoprotein lipase on my hand um
19:28within that part of my body. I do have
19:30lipoprotein lipase for example on my
19:32belly and that's of course largely
19:34because I'm a man. But even still, as
19:36the triglyceride rich lipoprotein is
19:38flowing through the blood, like VLDLDL
19:40or LDL especially, where we have
19:42lipoprotein lipase is where we're
19:44generally going to store more fat. And
19:46in the very next segment in just a
19:48moment, we're going to talk about the
19:49genetics and the environmental factors
19:51that play into it. But in addition to
19:54fat contributing to fat storage, of
19:56course, we have one other one. It's not
19:58going to be proteins or amino acids.
20:00It's going to be glucose. Fat can
20:03convert glucose into fat very very well.
20:06Anyone who tells you anything
20:07differently than that is wrong. The fat
20:10cell is perfectly capable and even
20:12delighted to take in glucose and turn it
20:16to fat. What is essential in this
20:19process is in fact insulin. Insulin is
20:22essential at allowing a fat cell to
20:24store more fat.
20:26The evidence for this is so obvious. Not
20:29only in fat cell cultures, as I've
20:31elaborated on before, we have fat cells
20:34growing in my lab literally right now.
20:36And they're surrounded by fats and
20:38glucose, all the energy they would need
20:40to get big. And they will stay very
20:42small, skinny little fat cells until we
20:45spike insulin into the culture. When we
20:47put insulin in, now the fat cells know
20:50what to do. And that is to promote
20:52overall the storage. And insulin is
20:55absolutely critical. Even in the case of
20:58a whole body, if you have a person with
20:59type 1 diabetes, they can eat whatever
21:02they want and they need only to skip or
21:06deliberately underdose their insulin
21:08injections and they will be as thin as
21:10they want. There will not only be no
21:12lipogenesis, which is the synthesis of
21:14new stored fat. There will also be
21:17nothing to turn off lipolysis, which is
21:20the breakdown of fat. And that's where
21:22insulin is particularly powerful um at
21:25inhibiting lipolysis. So preventing the
21:28breakdown, forcing the fat cell to hold
21:30on to whatever fat it's storing.
21:33There is of course genetic
21:34predisposition. It's not that you're
21:37going to have a specific gene or the ex
21:40or a variant of a gene that's going to
21:41determine how much fat, but rather even
21:44though there are some genes that are
21:46very much influential there like MC4R
21:50or leptin. Um, but these are mutations
21:53that are very uncommon. This is not your
21:56garden variety. I'm gaining weight or
21:58I'm even obese. There's no distinct
22:01genetic mutation in in the average
22:03version of having too much body fat, but
22:06there is clearly something familial
22:08about it. Even if there's not a distinct
22:11genetic pattern, if mom and dad are
22:13overweight or obese, it's very likely
22:15offspring will be too. Now, you can
22:17already see the conflict with regards to
22:19environment. You know, the same
22:21environment that's making mom and dad
22:23obese is going to be the same
22:24environment that this child is being
22:26raised in. But even beyond that, there
22:28is in fact a familial inheritance to
22:30this um not only determining how much
22:33body fat gets stored but also even where
22:37a person is storing fat. If you are
22:40someone who struggles with fat and you
22:42look at your parents or siblings and
22:44they do too, this is just going to be
22:46something that is more of a struggle. Um
22:49there are of course um dietary
22:51influences and indeed I would say these
22:53are the most relevant. Um but uh it
22:58perhaps the most succinct way of
23:00describing the relevance of diet is that
23:02there must be two conditions that are
23:04met to promote the storage of fat. You
23:08cannot have fat storage with only one of
23:11them. um you have to have both and those
23:16are elevated insulin and sufficient
23:19energy.
23:21Now that latter point I understand it
23:23perhaps comes off as a little vague. So
23:25let me explain it in the context of the
23:27first point sufficient insulin as I
23:30somewhat elaborated on a moment ago.
23:32There can there can literally be no fat
23:35storage on a human or any animal unless
23:38insulin is elevated. It cannot happen.
23:41It is impossible and and unless you
23:43think well Ben what about all those
23:45other maybe a person ate a thousand
23:48calories in excess. If insulin is low
23:50the body will compensate for that excess
23:53by both increasing its metabolic rate
23:55substantially by several hundred
23:57calories if insulin is low and it will
24:01um start wasting energy from the body in
24:03the form of producing ketones. Remember
24:05every ketone has a caloric value roughly
24:07comparable to glucose. And when you're
24:09in ketosis, you're breathing out those
24:11ketones or urinating out the ketones.
24:13And if the problem got so bad, then
24:15glucose levels get so high that glucose
24:17is also spilling out into the urine. So
24:20the body has ways to compensate to
24:22reconcile this. But again, if insulin is
24:25low, there's no potential for fat
24:27storage. Now, if insulin is high, there
24:30is the signal for fat storage. But
24:32insulin itself is not energy. It's not
24:34the hydrocarbons that are capable of
24:36being stored as fat within the lipid
24:38droplet of a fat cell. And that's where
24:40the second point comes in. It's one
24:42thing to tell the cell to store fat,
24:45which is what insulin is doing. And why
24:47that is a drum I beat so loudly. A fat
24:50cell, like every cell, must be told what
24:52to do with the energy that's available
24:54to it. Hormones do that, particularly
24:57insulin. So again, it's one thing to
24:59tell the cell to store fat, but it's
25:01another to actually have the
25:02hydrocarbons or the calories to say it
25:04another way to actually fuel that
25:07storage. And that's where the sufficient
25:09energy or sufficient calories comes in.
25:12So you must have an insulin stimulus to
25:14store the fat and you must have
25:16sufficient calories to fuel that storage
25:18or provide the bulk of the storage. And
25:21then physical activity, exercise is
25:23generally irrelevant to be frank. One of
25:26my hopefully clever quips is that you
25:30eat smart to be lean, but you exercise
25:32to be strong. And so there's not really
25:34much to say. Ex studies that have looked
25:36only at physical activity um find that
25:39it it's generally a big failure. Uh and
25:42that's in part because if you exercise
25:44more, not only are you actually burning
25:46a fantastically small amount of calories
25:49of energy, but then you also compensate
25:51usually by getting a little hungrier the
25:53next day or so. Maybe not immediately
25:56after, within the first few hours, but
25:58give it a little time and your hunger
25:59will go up.

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