It’s time for the season finale! Next week I will pivot to discussing my personal results of using sterculia oil to inhibit SCD1. In this post I will summarize my posts on the topic to date before bringing the thread to a near term conclusion using an example that in retrospect will be so obvious that you’ll kick yourself for not having guessed it: the Syrian hamster, a food-storing hibernator.
The story of the Syrian hamster and the way it juggles its metabolism to hibernate is a beautiful narrative example of the topics covered in this thread. The teaser version is that to get into a state of deep torpor – low metabolic rate, lowered body temperature – it elevates SCD1 and PPAR gamma. Does this sound like anyone you know? Once the hamster reaches the state of deep torpor it becomes very good at maintaining its fat mass with very little food.
Deep torpor is a state that many mammals have the ability to go into: dormice, hamsters, bears, bats, woodchucks, chipmunks, lemurs, hedgehogs, skunks, and on and on. This suggests that the basic metabolic tools to get into deep torpor were in place before mammals branched off of the evolutionary tree. If you’re reading this you’re likely to be a mammal. Are you in deep torpor?
Before we jump into it, let’s make sure everyone is up to date.
Summary Of The SCD1 Theory Of Obesity To Date
So far, in this season of Fire In A Bottle:
- The SCD1 Theory Of Obesity Part One: Leptin is a hormone released by fat cells. As you get fatter you make more of it. The job of leptin is to increase the rate of fat burning which drives mitochondrial Reactive Oxygen Species (ROS) production. Mitochondrial ROS suppresses production of SCD1, whose job is to turn saturated fats into monounsaturated fats. When your fat becomes too unsaturated, you fail to generate ROS production. If you generate enough ROS your fat cells will go through a process called browning, which leads to thermogenesis – a process by which you burn calories off as heat. If you make too much SCD1, your fat won’t be saturated enough to do this and you will stop responding properly to leptin. It has been shown very clearly that mice who lack leptin become very fat but that if they ALSO lack SCD1 they are nearly as lean as mice who have leptin. Leptins main job is to suppress SCD1. Things that lack SCD1 fail to store fat and things that make lots of SCD1 get fat, including Native Americans living an ancestral lifestyle but eating nothing but maple sugar.
- The SCD1 Theory of Obesity Part 2: A LOT of ROS inhibits SCD1 but a LITTLE ROS increases it. The consumption of too much linoleic acid (LA), a common omega 6 polyunsaturated fat (PUFA), leads to a LITTLE mitochondrial ROS production. This leads to SCD1 being upregulated which leads to your fat being unsaturated which leads to a little ROS which leads to more SCD1. A positive feedback loop of unsaturation and failure to do thermogenesis. This is the post-obese metabolism. Many of us are in this boat. You can diagnose this using a blood test that measures the amount of oleic and stearic acid in your red blood cell phospholipids. Just divide oleic by stearic to get your Desaturase Index (DI). A lower DI is better. Things that suppress SCD1 include fish oil, CLA, metformin and berberine. Sterculia oil, from a tropical tree seed, blocks the enzymatic activity of SCD1.
- Membrane Phospholipid Composition of Different Populations shows that an ideal DI might be as low as 1.1.
- Dietary Monounsaturated Fat, The SCD1 Theory of Obesity, Part 3: There is a mechanism that the metabolism uses to cope with dietary monounsaturated fat (MUFA), which cannot be stored as is lest it trigger the post-obese metabolism. Oleic acid is turned into a signalling molecule called OEA in the intestine, which activates a transcription factor in fat cells called PPAR alpha AND it downregulates SCD1. PPAR alpha upregulates all areas of fat metabolism: lipogenesis, fat transport and fat oxidation. In this way saturated fat is produced to “up-saturate” the MUFA before it can be stored. The first pantry items in Africa 170,000 years ago were stored marrow bones and potato like tubers. Bone marrow is mostly MUFA. When eaten together, the starch from the tubers would have provided substrate for saturated fat to be produced to be blended in with the marrow fat.
- Pu’erh Tea is a potent Suppressor of SCD1: pretty much what it sounds like.
- This is Your Body Temperature on Vegetable Oil introduces a Bolivian population who had a well documented 1 degree F drop in body temperature since 2004. In 2004 they ate what they grew – manioc, plantain and rice: mostly starch – and had the classic body temperature of 98.6. A store was introduced after that giving them access to vegetable oil. A mouse model shows how adding PUFA to a starch based diet can cause a dramatic body temperature drop by lowering the amount of uncoupling protein (UCP1) that is produced which allows for mitochondrial uncoupling and adaptive thermogenesis – the ability to burn off calories as heat. The body temperatures of peoples of the industrialized world have dropped since the industrial revolution while vegetable oil consumption has risen.
- Speed Your Metabolism With Oxidative Stress! Slow It With Antioxidants! Mice lacking Nrf2 – the transcription factor responsible for antioxidant response – have frank oxidative stress, a high metabolic rate and resistance to obesity. Without the ability to reduce hydrogen peroxide, they are forced to produce uncoupling protein. This makes their metabolism “inefficient” – they burn off their calories as heat rather than storing them as fat. It’s funny. If you give them antioxidants, they no longer are forced to uncouple and they get fat.
- Native Americans Removed Acorn Oil and Replaced It With Bear Fat: There is documentary evidence that Native Americans removed the (relatively high PUFA) oil from acorns – a dietary staple. Yet they had no problem combining animal fats with starch from acorns, corn, and native potatoes and wild rye.
- The Body Fat Of Starch Eaters is Highly Saturated; Linoleic acid Dysregulates SCD1: Starch eating cultures have very saturated bodyfat. This explains this quote from the authors of the original China Health Study, “In the China Study, the least active Chinese consumed 30% more calories than their American counterparts yet their body weight was 20% lower. The excess calories were lost as heat rather than being stored as fat.” Regulation of fat saturation seems very robust up to a level of around 6% of calories from linoleic acid. Americans had relatively saturated body fat in 1962. By 1991, dietary and stored PUFA levels had risen substantially, and the desaturase index (DI) had greatly increased in parallel. By 1991, LA consumption had dys-regulated American SCD1 levels.
- Bear Hunting Season; Native Americans Hunted Bear When The PUFA Content Was Lowest: Bear fat was a Native American staple. Instead of hunting bear in the fall when the bear were the fattest, they waited until late winter to hunt bear – when the PUFA content of the fat was the lowest. A winter staple food was roasted venison dipped into a sauce of bear fat and maple sugar mixed so that it nearly as sweet as pure maple sugar. There is no evidence that Native Americans got fat from this , unlike those eating pure maple sugar.
- Fat Newborns; Sloth and Gluttony Part 1. The desaturase index of mother’s blood is strongly associated with newborn BMI and up until 2 years of age. This is independent from the blood sugar or insulin levels of the mother. Since these are newborns we know they didn’t become obese by overeating or couch-potatoism.
- Good PPAR, Bad PPAR. It can be clearly demonstrated in mice that feeding them a diet of 10% linoleic acid dys-regulates their fat metabolism, increasing PPAR gamma and decreasing PPAR alpha. PPAR gamma upregulates SCD1 and Elovl3. The end products of SCD1 and Elovl3 upregulate PPAR gamma. Positive feedback loop again. This mouse study is an exact parallel to what happened to humans in America between 1962 and 1991 as chronicled in The Body Fat Of Starch Eaters. PPAR gamma makes humans fat and PPAR alpha causes weight loss in humans.
- Very Long Chain Saturated and Monounsaturated Fats are another indicator that your SCD1-PPAR gamma-Elovl axis is dysregulated. High levels of them are associated with increasing severity of diabetic retinopathy, Major Depressive Disorder and Psychosis.
The bear is an interesting model – a large mammal, monogastric omnivore who enjoys salmon and berries. Again, sound like anyone you know?
We’ve already seen that the PUFA content of bear fat peaks in the fall, before hibernation. Is this coincidental to the availability of acorns – a source of LA – or is it actually functional. This review1 on the use of polyunsaturated fat by hibernators is quite clear that polyunsaturated fat enhances torpor:
Heterothermic mammals increase the proportion of polyunsaturated fatty acids (PUFA) in their body fatsDaniel Munro, Donald W. Thomas
prior to entering torpor. … Low-PUFA diets consistently increase the lower setpoint for body temperature and minimum metabolic rate for both hibernators and daily heterotherms. Above the lower setpoint, low-PUFA diets usually increase body
temperature and metabolic rate and decrease the duration of torpor bouts and this effect is similar for hibernators and
In hibernators, just like starch eating Bolivian humans, a low-PUFA diet increases body temperature and metabolic rate.
The other thing that can decrease metabolic rate is the over-expression of SCD1, which turns saturated fat into unsaturated fat. Do hibernators make more SCD1 during torpor? This study2 shows that bears have a ratio of monounsaturated fat to saturated fat (a less specific type of DI than comparing oleic acid to stearic acid) of 1.09 in June and 1.55 in February, highly suggestive of an increase in SCD1 during torpor in the hibernator most like us.
To get into torpor, bears increase the amount of PUFA in their stored bodyfat and upregulate SCD1, just like Americans did between 1962 and 1991.
It may not be shocking that hamsters are easier to study in a lab than bears. This 2019 paper3 does a beautiful job of detailing the metabolic changes that take place in the Syrian hamster as it goes through hibernation. The stimulus for the hamster to hibernate is a reduction in temperature. They make it cold. The hamsters go through 12-15 weeks of metabolic changes before going into deep torpor. These hamsters hibernate with food. Every five days or so, they increase their body temperature, wake up and eat a little, then they drop back into deep torpor. This is a graph of their body temperature.
This model is a beautiful narrative framework for most of the topics covered in this thread: PPAR gamma and alpha, SCD1, UCP1 and therefore mitochondrial uncoupling and metabolic rate, and how all of those things relate to body fat levels. I’ll explain it in narrative fashion, then I’ll show you the graphs, then we’ll go through it again.
First some definitions: iWAT is inguinal white adipose tissue, a type of abdominal fat. Ppara is PPAR alpha. Ppargc1a and Ppargc1b are PPAR gamma co-regulators – a rough indicator of overall PPAR signalling. Non-HIB is non hibernating, SD-cold is when the temperature has been lowered and the animals are getting ready to hibernate, HIB-PA is the portion of hibernating while the animals body temperatures are higher and they’re awake, HIB-DT is deep torpor – low body temperature hibernation – and Post-HIB is post hibernation.
When the hamster is in non hibernating mode, PPAR alpha is low as well as PPAR activity in general. SCD1 levels are very low, but UCP1 levels are also very low due to lack of PPAR signalling. The hamster has a relatively high amount of bodyfat.
When the temperature drops, PPAR activity increases a little (light blue on the heat map is more activity than dark blue). SCD1 activity is still low, so the increase in PPAR leads to a large rise in UCP-1. The body temperature drops immediately – hamsters have a high surface to volume ratio and are affected dramatically by heat changes – but then stays stable until around the 40 day mark. During this time period – high UCP-1, low SCD1, moderate PPAR, stable body temperature – the hamsters lose significant body fat.
At the 40 day mark, the body temperature of the hamsters starts to drop steadily. SCD1 increases, UCP1 drops to almost zero and the fat mass of the hamsters is totally replenished by the twelth week. So with high SCD1 and low UCP-1 we have fat gain.
The animals go into deep torpor. SCD1 is at its highest point, PPAR alpha is a low percentage of overall PPAR signalling, UCP-1 is low and the body temperature and metabolic rate of the hamsters plummet.
Now it is time to wake up and eat. SCD1 levels drop a little and PPAR alpha levels are raised to the highest. UCP-1 levels go up. Body temperature rises. Remember than when SCD1 levels were very low a small increase in PPAR alpha lead to a large increase in UCP-1? Now that SCD1 levels are quite high, a large increase in PPAR alpha leads to a small increase in UCP-1.
- When SCD1 is low a small increase in PPAR signaling creates a large rise in UCP-1 and metabolic rate
- Body fat decreases when UCP-1 levels are high.
- Body fat levels rise in parallel with increasing SCD1
- When SCD1 levels are high, a large increase in PPAR alpha only leads to a small increase in UCP-1
SCD1 Is Increased by PPAR Gamma and Delta but not Alpha
Fat cells were removed from the hamsters and cultured with either DMSO – a negative control, fenofibrate – a PPAR specific agonist (it turns it ON), L-165041 – a PPAR delta specific agonist or rosiglitazone – a PPAR gamma specific agonist. When the hamsters are in non-hibernation, activating PPAR gamma or PPAR delta substantially increase SCD1. Activating PPAR alpha does not increase SCD1. When the hamsters are in hibernation mode, SCD1 is high no matter what!
Deep torpor is a metabolic state that is widely distributed through the mammalian family. It is enhanced by the consumption and storage of polyunsaturated fats, in particular linoleic acid. Molecular changes that occur during deep torpor include increased expression of SCD1 and high activity of the PPAR transcription factors with a relatively low contribution from PPAR alpha. Metabolic changes during deep torpor include low body temperature, low metabolic rate and the ability to maintain body fat levels with relatively few calories.
American consumption of linoleic acid increased dramatically between 1962 and 1991. Our stored levels of linoleic acid increased, as did our desaturase index, indicating up-regulated levels of SCD1. Recent blood tests from myself and many of you show high levels of very long chain saturated and mono-unsaturated fats, suggesting that we have very high levels of PPAR gamma. The body temperature of Americans has dropped over the last 150 years. We have become very good at maintaining our fat mass.
Are you in deep torpor?
- 1.Munro D, Thomas DW. The role of polyunsaturated fatty acids in the expression of torpor by mammals: a review. Zoology. Published online March 2004:29-48. doi:10.1016/j.zool.2003.12.001
- 2.Giroud S, Chery I, Bertile F, et al. Lipidomics Reveals Seasonal Shifts in a Large-Bodied Hibernator, the Brown Bear. Front Physiol. Published online April 12, 2019. doi:10.3389/fphys.2019.00389
- 3.Chayama Y, Ando L, Sato Y, et al. Molecular Basis of White Adipose Tissue Remodeling That Precedes and Coincides With Hibernation in the Syrian Hamster, a Food-Storing Hibernator. Front Physiol. Published online January 28, 2019. doi:10.3389/fphys.2018.01973