Hi Reddit!

We are a team of scientists based in the Metabolic Research Laboratories, University of Cambridge. Our primary research focus is to understand the genetic and environmental factors influencing the function of white adipose tissue (fat). We think that appropriate function of fat tissue is central for human health. Impairments of fat tissue function cause nutrient deposition elsewhere in the body, leading to the development of type 2 diabetes, hearth disease and other related disorders.

Currently, the diagnosis for type 2 diabetes is based on fasting blood glucose and oral glucose tolerance test. These factors indicate how well pancreas secrete insulin, and how well the glucose is taken up from the circulation in response to secreted insulin. Importantly, impairments in either of the processes is a sign of advanced metabolic disease, when clinical and lifestyle interventions are much less effective than early measures directed to prevent disease development.

We have recently published a paper showing that mice with dysfunctional fat tissue exhibit normal glucose metabolism when they are young. However, they become much more insulin resistant when they get older compared to control mice. The impaired function of fat tissue in these mice at a young age cannot be identified using glucose tolerance test, but can be easily spotted after they eat too much of their regular food. We therefore think that a mixed nutrient tolerance test (in other words - a large meal) could identify individuals with impaired fat tissue function, and would encourage clinical or lifestyle interventions while their glucose metabolism is still normal.

Ask us anything related to the role of fat tissue, fat metabolism and nutrition, and we will do our best to answer your questions!

Proof: https://twitter.com/TVPLab

Link to the original research paper (Open access): https://tinyurl.com/y7tmxyc4

Link to the lay summary of the paper in 'The Conversation': https://theconversation.com/diabetes-new-test-could-detect-the-disease-much-earlier-101409

Edit1: Fixed the link to the paper.

Comments: 63 • Responses: 21  • Date: 

ninjamullet20 karma

Do you get criticism from "health at every size" activists (or other people who might simplify your conclusions as "fat causes lots of diseases") and how do you respond to them?

TVP_lab26 karma

We haven't received any criticisms from activists so far, and hopefully we won't in future! As scientists, we are not trying to push any public agendas, but simply to construct hypotheses and try to answer them in a scientific manner.

Another important point here is that the amount of fat in any given individual will not directly pose a risk of disease. There are some individuals that have a lot of fat, but as it is functioning properly, they are metabolically healthy! Conversely, there are some slim individuals with very little or no functional fat tissue that are very insulin resistant.

Sam from our group wrote a review a while ago titled 'It's Not How Fat You Are, It's What You Do with It That Counts'. We still think this statement holds true!

Link to review: http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.0060237

Kasparas

therealplanetx12 karma

Can you explain or provide a link to an explanation of how fat cells work? What dietary intake leads to storage in fat cells? What prevents fat cells from releasing their stores? What dietary intake allows fat cells to release their stores?

TVP_lab21 karma

Hey the realplanetX

This is a great question.

Fat cells have three major functions:

  1. They store calories long term. A Kg of fat has more than twice the calories as a Kg of carbs or protein. This means if you need to cart around an energy store it is more efficient to use fat than other types of storage molecule.
  2. Fat cells secrete loads of hormones that control different aspects of how our bodies work. For example, the hormone leptin is produced by fat cells. It tells the body if it has enough nutrients to do certain things, for example if you have really low leptin levels women temporarily cease being able to reproduce. This would have evolved to prevent animals getting pregnant when you lack enough fat reserves to support the pregnancy.
  3. Fat cells buffer our daily lipids. After we eat insulin tells fat cells to take up the fat we have eaten and store it. We can then burn the carbohydrate parts of our meals. Then, when we are asleep the nervous system tells fat cells to break down and release it into the blood stream. These fatty acids that are released by adipose tissue can then be used by organs like muscle and heart for fuel.

In this article we focus on aspect 3 - fat cells as lipid buffers.

Cheers,

Sam

coryrenton9 karma

is fat tissue typically dysfunctional throughout the body or does it tend to be localized in specific areas -- if so, would transplantation from healthier deposits help mediate the dysfunction?

TVP_lab8 karma

Hey coryrenton,

This is another great question.

Firstly, how much fat you have in different areas is really important. Generally you can think of fat as being either subcutaneous (below the skin but outside the cavities where the organs sit) or visceral (inside the abdomen where the guts and liver are). The current view roughly breaks down as

visceral fat more is bad for you

subcutanous fat on the upper body (above the waste) is probably neutral

subcutaneous fat on the lower body is actively good (ie the fatter your thighs and bottom are the better for you!!!)

One idea is that visceral fat only accumulates when subcutaneous fat fails, so it is the failure of the good fat that is important rather than the accumulation of the bad fat (which just follows the failure of the good fat!).

Transplant studies in mice are mixed, but some do suggest transplanting healthier fat improves metabolic outcomes. I don't think there is a definitive answer.

Cheers,

Sam

coryrenton2 karma

Do you see evidence of people preferentially accumulating visceral fat over subcutaneous fat after a period of dropping to a very low body fat percentage, then resuming a normal caloric intake (along the lines of reasoning that there isn't enough subcutaneous fat to maintain health)?

TVP_lab11 karma

Hey coreyrenton,

This is an interesting idea. There are suggestions out there that yo-yo dieting (ie losing then gaining weight repeatedly) may be bad for you, but I hadn't thought about it impacting on adipose tissue depots differently.

We haven't done this personally, but I had a quick look at the literature there are a few studies out there suggesting weight loss and regain can affect body fat distribution. Some other studies suggest that this does not happen, so it seems that it is not currently clear.

However, if I understand what you are asking, when we lose weight we don't necessarily lose fat cells- the cells have a half-life of about 8 years. What happens is the cells shrink as they empty of fat. They can then refill.

Cheers,

Sam

swingerofbirch7 karma

What exactly can be spotted earlier on after the mixed meal test? Are you still using glucose/insulin as biomarkers as in an OGTT or something else? If glucose/insulin, wouldn't those rise less in a mixed meal test than a traditional glucose test?

And are you saying it's the inborn, inherent nature of an animal's fat that controls the development of metabolic disorders or that it's associated with these disorders?

TVP_lab4 karma

Hey Swingerofbirch,

Sorry to not reply earlier.

Yes we would use glucose/insulin like an OGTT.

Would the rise be smaller? In a healthy individual it should be, as fat would be stored and there would be less glucose in the challenge.

However, we think in people with defective fat they would be primed to use glucose when fasted, as their fat would not release lipid and they would be burning glucose. We do an OGTT when fasted, so then they are being given glucose precisely when their body is set up to use glucose. Conversely, if we use a mixed meal the adipose cannot take up the fat, the fat is directed to muscle and then it causes transient insulin resistance, raising glucose and insulin.

Furthermore, caloric equivalents here are important. A lot of people use MMTT scientifically, but the most common size is 600 calories. If everyone ate three meals of 600 calories a day there would be very little obesity/diabetes. We think a larger size of meal would be more suitable in this test.

Finally, we know there are genetic factors controlling adipose tissue function - see this article https://www.ncbi.nlm.nih.gov/pubmed/21706003. However, we also know that the more obese people become the less well their fat works https://www.ncbi.nlm.nih.gov/pubmed/20943748.

So the answer is a bit of both - if you have bad fat you may become metabolically ill at a lower BMI, however the fatter you get the more likely you are to have your fat become dysfunctional.

Cheers,

Sam

Hendrikto5 karma

I weighed 135kg at one point. Back then I exclusively drank sweet stuff like ice tea, Coke, Sprite, … I was getting fatter and fatter.

About two years ago I decided that something had to change. I did not alter my dietary patterns, I did not begin to exercise. Literally the only thing I changed was my drinking habits. I switched to drinking exclusively water. Within a year I lost 25kg and I am nearing 50kg (loss, meaning I weigh ~85kg now).

My questions are:

  1. Have you heard of cases like this before?
  2. What do you think caused this? My guess is that I never ate unhealthy, but the constant sugar intake held me in the “glucose metabolism phase”. Without the constant sugar my body actually uses its fat instead of just stockpiling it.
  3. Do you think we should mandate warnings on these sweet drinks similar to tobacco?

TVP_lab9 karma

Hey Hendrikto

  1. I am not a medical dr, so I don't come across individuals who have lost a lot of weight!

  2. Physics caused this. 25 kg of fat is about 55kg of pure sugar! So that is about 550 litres of coca cola.

If you were drinking that about a 1.5 liters of coke a day (which based on your post sounds likely if you were drinking only sugary drinks) then you were consuming 150 grams of sugar, or 600 calories just from the drinks.

If you stopped consuming the 600 calories a day without changing the other aspects of your diet you could lose that much weight.

Cheers,

Sam

dranktoomany5 karma

Im still reading and digesting. You mention that "our data suggest that “murinizing” human feeding patterns may be a way to treat individuals with adipose dysfunction and storage defects.". I'm a type 2 diabetic who has taken a high a1c to a very low number with no medication through the ketogenic diet and use of fasting. I'm led to believe that frequent feeding would likely cause more insulin resistance and have restricted my eating windows to 8 hours or even once a day to help minimize insulin resistance. Do you think frequent feedings could potentially be counter productive?

TVP_lab4 karma

Hey dranktoomany,

Firstly I want to stress I am not an MD, but a PhD so I cannot comment on your specific medical issues.

One of the major ways both ketogenic diets and limited windows of eating (aka intermittent fasting) work is by reducing caloric intake and therefore driving weight loss. Weight loss will improve adipose function and diabetes. (I discuss this in some of my other posts (see Luuna_tic).

While this is speculative, an area my colleague Kasparas is interested in is if intermittent fasting can improve adipose tissue function by essentially "exercising" fat (making it store a lot, then release a lot).

However, we think its possible that some individuals may not benefit from the intermittent fasting as their fat is too dysfunctional. For these individuals then frequent small meals (and SMALL is important - you cannot eat 6x600 calorie meals or you will get more obese and potentially more insulin resistant) may be better. We don't know if this will work in humans yet, but we think it is important to investigate.

Overall, we think different people may benefit from different diet regimes. If what you are doing is working for you I would suggest you stick with it unless advised otherwise by your physician.

Sam

TVP_lab3 karma

Good question! One of the key points of this paper is that 'murinized' feeding patterns could be beneficial if your fat tissue cannot cope with the heavy nutrient loads imposed by large infrequent meals.

However, if your fat tissue can take up and release nutrients appropriately (which it should in most individuals), then why not utilise it for its designed purpose? More and more research in mice and humans now show that feeding patterns consisting of fewer large meals, and prolonged fasting periods in between meals (intermittent fasting) lead to multiple metabolic health benefits, compared to more frequent and smaller meals. If you observed improvements in your health after switching to intermittent fasting (I certainly did), then stick to it!

Kasparas

Bokbreath5 karma

How do you define ‘dysfunctional fat tissue’ ?

TVP_lab13 karma

Hey Bokbreath,

There are several ways fat can be dysfunctional, but what we focus on in this paper is its daily role in controlling what the body does with the fat you eat.

Healthy fat (adipose tissue) takes up the fat we consume and stores it until it is needed for fuel, such as at night when we are asleep. When obese people eat a meal their adipose tissue does not take up the fat. Instead, the fat is directed into other organs, such as the liver and muscle where it causes insulin resistance.

Importantly, the adipose tissue of obese people is also bad at releasing fat when they are asleep, meaning that obese people have to use lots of glucose when they are sleeping to provide energy.

So fat that is dysfunctional is bad at both taking up and releasing fat, leading to the body using the wrong nutrients at the wrong time.

Sam Virtue

Oyvas5 karma

Do you think white fat “browning” has potential for widespread application for weight loss/metabolic improvment?

TVP_lab9 karma

Hey Oyvas,

Absolutely- we are also working on that in the lab. One important point about making white fat browner (or beiger) is that it is not enough to just have bat, you need to be able to activate it (pharmacologically or with nerves) and provide it with fuel (with a good blood supply). Think about it as like putting a giant engine in a car. It won’t do much unless you connect the fuel supply and the accelerator peddle!

Sam Virtue

luuna_tic3 karma

Have you heard of Dr. Neal Barnard?

Just from his website, “Dr. Barnard is a fellow of the American College of Cardiology, the 2016 recipient of the American College of Lifestyle Medicine’s Trailblazer Award, and has led numerous research studies investigating the effects of diet on diabetes, body weight, and chronic pain, including a groundbreaking study of dietary interventions in type 2 diabetes, funded by the National Institutes of Health.”

He’s reversed type 2 diabetes in hundreds of his patients by teaching them how to adopt a plant based lifestyle that is low in fat. He’s shown the correlation between diets high in animal protein /fat and type 2 diabetes.

What would you say to this?

Also, sorry if I sound silly, hehe. I’m vegan and have read books/watched videos by plant based doctors such as Dr. Neal Barnard and I find his research fascinating, though I do find it difficult to understand some of the more ... “advanced medical talk”. I just think that anyone studying diabetes should definitely check out his work as he’s been researching it for a few decades (since the 80s) and has first hand experience in helping people reverse their type 2 diabetes by changing their diet to a low fat plant based one.

Thank you for doing this ama!

TVP_lab3 karma

Dear Luuna_tic,

I am not familiar with Dr Neal Barnard's work so I can't comment on it directly.

What I would say is that a diet high in vegetables, vegetable oils and vegetable proteins (nuts, seeds, pulses) is generally a pretty healthy diet.

It is of course possible to eat healthily while consuming meat, fish eggs and dairy, however most junk food will have a lot of meat and dairy in it. Therefore a lot of the available high protein/high fat food is unhealthy. However, it is not the case that eating meat/dairy need be inherently be unhealthy.

There is other evidence that type 2 diabetes can be ameliorated or even partly reversed by extreme dieting https://www.ncl.ac.uk/magres/research/diabetes/reversal/#publicinformation.

What we do know, however, is that lot of people find diets difficult to stick to.

Cheers,

Sam

gaspanicc3 karma

Hi,

This is an extremely interesting and exciting topic you guys are researching. Diet is one of the fundamental ways in which we prevent getting many of the leading causes of death (heart disease, diabetes etc). Although diet/food is essential for life, it is often overlooked at how powerful a healthy diet can be to prevent leading diseases.

I just have a couple questions.

1) Even if you are slightly under your caloric baseline for gaining/losing weight, but are eating a diet high in saturated fats, can you still gain weight? For instance, if I need to eat under 2000 cals a day to lose weight, and I eat 1700 calories in bacon and McDonalds, can I still gain weight?

2) Many people are a fan of the keto-diet: a diet low in glucose and high in fat. Is there a stress difference on your body between using ketones as metabolic fuel vs. glycogen?

3) How much easier is dietary fat stored as body fat compared to carbohydrates?

Super cool AMA. Sorry for rush of questions

Thanks

TVP_lab5 karma

Hey Gaspanicc,

We like the topic too!

  1. This is a physics question. If you eat 1700 calories (no matter what they are made of) and you burn 2000 then you will lose weight. However, if you eat very calorific foods you have to have tiny portions, which some people find unsatisfying. Also, depressingly, you will only lose weight until your body has reduced in size to the point where 1700 calories is now your daily requirement!
  2. I am not an expert on the Keto diet - Kasparas has more interest in this. I'll ask him to comment on some of the Keto questions.
  3. Great question. So dietary fat can be stored directly. And if fat works well, when you eat almost all the fat you eat should be stored and your body burns the carbs. However, if you eat a very high carb diet you will start to turn carbs into fat and store these. The fats your body makes from carbs are slightly different to dietary ones, however, to my knowledge they are stored equally well, but this is not a very well researched area!

Sam

ironlabel13 karma

What is the fastest way to decrease fat tissue in the body?

TVP_lab7 karma

Hey ironlabel1

This is a physics question. To reduce fat you must either increase your energy expenditure or reduce your food intake. From a time perspective reducing the number of calories you eat is easier for most people than greatly increasing their levels of physical activity.

Cheers,

Sam

ImmigrantNo12 karma

How do we kill these..fat cells?

TVP_lab6 karma

Hey ImmigrantNo1,

Killing fat cells is a bad idea. People with no fat (a disease called lipodystrophy) get really bad diabetes. We think obesity makes fat stop working properly- so it is like having no fat, just not as severe.

Check out the link in the Conversation piece for more info.

Sam

causalcorrelation2 karma

Do you find that the adipose tissue responds differently depending on the type of fat consumed?

Also, your link is broken :/

TVP_lab2 karma

Hey casualcorrelation,

We have changes the link to a TinyUrl, hope that sorts it.

How types of fat interact with adipocyte storage and release is an interesting topic and is still unclear. Whether specific fatty acids ard better or worse for fat function, or if what we see in fat fat simply reflects what has been consumed needs to be clarified.

Sam

mngooselord2 karma

Do you know of any risk factors that might trigger adipose tissue dysfunction? e.g. lifestyle, environmental (medications, exposure to endocrine disruptors, consumption of advanced glycation end products, etc.)

Is there anything we can do at an individual level to improve adipose tissue function?

TVP_lab2 karma

Hey mngooselord,

Eat a healthy balanced diet, do exercise and lose (or at least stop gaining) weight will make you healthier. Whether this will directly improve adipose function or not is not entirely clear but it will make you metabolically healthier and your adipose tissue will be healthier too.

Cheers,

Sam

Alexbrainbox2 karma

Is there any indication that manual removal of fat tissue (eg. by liposuction) would improve health outcomes?

TVP_lab2 karma

Dear Alexbrainbox,

Not really. A lot of studies have looked into this. Most have been neutral or found a detrimental effect. Physically removing fat means you have fewer cells to do the job and so they become overworked.

Cheers,

Sam

sandleaz1 karma

Are you on keto diets?

TVP_lab1 karma

Dear Sanleaz,

I am not.

Sam

bisteccafiorentina1 karma

What factors are known to impair function of adipose tissue?

TVP_lab1 karma

Dear bisteccafiorentina,

Your handle is making me hungry!

There are lots of factors. The most clear one is obesity - the fatter you are the more likely your adipose tissue becomes dysfunctional.

There is good evidence that stress hormones (particularly cortisol) can impair fat function.

Furthermore inflammation within fat has been shown to cause it to function less well in rodents. Human evidence is not as clear cut and whether systemic inflammation can impair it is also unclear.

People are now starting to look to see if exercise can improve fat function beyond just making your whole body healthier.

Sam

desert_dame1 karma

Does bad stress increase the accumulation of those bad fats around the abdomen? Been going through a year of hell the stomach grows but not so much the rest of me. A middle aged woman.

TVP_lab2 karma

Hey desert_dame,

A disease called cushings disease is associated with accumalting abdominal fat. It is caused by having very high levels of the stress hormone cortisol. However, the evidence that lower levels of cortisol (ie what you may see if you are very stressed) can also cause this phenomenon is less clear. Some people may be particularly sensitive to cortisol but we do not have solid evidence for this.

Sam

slpgh1 karma

Is there a test that I, as a consumer, ask my doctor to do today that can approximate this procedure? For instance, test non-fasting blood glucose?

I'm hitting my 40s and have been in the 90s for fasting glucose for at least 10 years. My doctor told me not to worry, but I have always been concerned that my age would push me over to the wrong and too-late side of things.

TVP_lab1 karma

Dear slpgh,

There is no test available yet. I would not suggest you try to approximate one. We need proper studies from clinician scientists to see how this will work in humans and then to define a sensible and controlled test if it proves valuable.

Best wishes,

Sam