Skim, semi-skimmed, or full fat latte?*

I am very pleased that you have chosen to join us here at Penny University on this very auspicious day… our official launch day!

[If you are reading this on any date after May 2^nd, 2013 then there is only one thing to say, “Where were you?  You missed it!  It was amazing!  There were fireworks and everything.  No really, seriously!**”  But thank you, nonetheless, for visiting the website and reading this post.]

I hope that you will enjoy everything Penny University has to offer (which, if you’re reading this on May 2^nd, 2013, is precisely one interview…  but what an interview!)

In the coming weeks you will be introduced to a number of intelligent, fascinating, and engaging PhD students, post-doctoral researchers, and early career researchers.  You will learn more about the newest research in archaeology, geology, and biology (among other subjects) than you ever thought was possible.  You will be educated.  You will have fun.  YOU WILL HAVE FUN!

Now, let me waste no more of your time, with no further ado, I present to you, our very first interview.

Oh, those fat cells in your latte? Don’t worry, they’re made with semi-skimmed milk!

Matthew Fenech is a Research Training Fellow in Diabetes and Endocrinology. He’s currently a PhD candidate at the University of East Anglia, and is also completing his clinical specialist training at the Norfolk & Norwich University Hospital. He’s interested in understanding why obese people are at such high risk of developing type 2 diabetes.

AA: So, tell us a little bit about your work:

MF: My PhD follows on from some work I had carried out earlier in my research training. I focused on two groups of really interesting proteins, called metalloproteinases (MPs), and tissue inhibitors of metalloproteinases (TIMPs). These proteins are interesting because we know that they have important roles in other diseases like cancer and arthritis, but little is known about their possible role in obesity. Broadly speaking, cells produce them to change the structure of their surrounding environment – a process known as ’tissue remodelling’. We know that fat tissue undergoes remodelling in obesity because, if you think about it, fat tissue can vary in size both from one individual to another, and throughout an individual’s lifetime.

My initial work showed that human fat cells produce these proteins, and that when the cells are in an ‘inflammatory’ environment, which is similar to fat tissue in obesity, then the production of MPs and TIMPs changes. We think that the inflammation seen in obesity causes fat cells to change their production of MPs and TIMPs, changing how fat tissue remodels, and leading to more fat being deposited round the waist (the ‘apple’ shape) rather than round the hips (the ‘pear’ shape). We know that ‘apple-shaped’ obesity carries a greater risk of type 2 diabetes and heart disease.

I’m now using a number of different techniques to try to find out exactly what these MPs and TIMPs do in normal fat tissue, and how this changes in obese fat tissue.

AA: Okay.  So it sounds like (in simple terms) all fat cells produce these proteins, but in an obese person these proteins act in a different way (than in a non-obese person) that ends up with even more fat being produced?

Before we move on to the details of your research can you explain a little bit more about fats cells and fat tissue?  I know we all have to have fat in order to be healthy, but are there different types of fat (you mention ‘normal’ and ‘obese’ fats)?  Do these start out as the same thing, but change because of the activities of these MPs and TIMPs?

MF: Fat (or ‘adipose’) tissue is actually a very useful tissue, as it’s designed specifically to store excess fat ‘safely’. If we don’t have adipose tissue, then any excess fat we eat ends up in tissues which aren’t designed to store it, like the liver. Here, it can cause a lot of damage, including conditions that can lead to diabetes and heart disease. In fact, there are people with genetic conditions that mean they can’t produce any adipose tissue at all, a situation called ‘lipodystrophy’. These patients are thin, but they become ill with severe diabetes, just like obese people. We now know it’s because they have no adipose tissue.

So how does this knowledge help us understand what’s going on in obese people? Well, although adipose tissue is excellent at storing fat safely, it has a limit on how much it can take. Just like any store, it eventually becomes full! When that happens, fat ‘overspills’ and ends up in in the abdomen (the ‘apple’ shape) and in other tissues and organs where it causes diabetes, just like in lipodystrophic patients.

Adipose tissue that’s full in obese people has a number of features that are different from adipose that still has some storage capacity left. ‘Full’, or ‘metabolically unhealthy’, adipose is inflamed and has large, ‘hypertrophied’, fat cells. On the other hand, ‘metabolically healthy’ adipose, such as what you might expect in thin people, is not inflamed and is largely made up of smaller fat cells.

Now – here’s the really interesting part. There are some obese people who don’t develop diabetes as expected for their weight. We think it’s because in these people, the adipose tissue has a larger ability to expand and mop up excess fat. And, tying in to my answer to the last question, this differing ability to expand between different people may be down to how the adipose tissue ‘remodels’. We think that in some people the remodelling is ‘healthy’ and allows more adipose expansion before fat overspills, whereas in others, the remodelling is ‘unhealthy’ and fat overspillage into the abdomen and other organs (e.g. the liver) occurs earlier. That’s where MPs and TIMPs may come in – just as they help with remodelling other tissues, they might be involved in this interesting remodelling process in adipose tissue, which in turn might explain why certain obese people develop diabetes and heart disease while others don’t.

We’re still at the very early stages of this research however. While we think that human fat cells grown the lab produce these MPs and TIMPs, we don’t know whether adipose tissue in healthy or ill individuals produce them, and whether different levels of these proteins actually lead to differences in the adipose tissue between healthy and ill individuals. So, a lot of work still to do!

AA: Wow, that is absolutely fascinating!  So people can actually be ‘thin on the outside and fat on the inside’ like we’ve heard mentioned a lot in the media recently?  And weight might not necessarily be an indicator of likelihood for developing Type 2 diabetes… it’s all down to the location of the fat and that in turn is down to the behaviour of their adipose tissue?

MF: Absolutely – ‘thin on the outside and fat on the inside’ is a good way to think about it. Weight is definitely an important indicator of the risk of developing Type 2 diabetes, but we’re recognising that it may not tell the whole story. In order to know more about one’s risk of developing type 2 diabetes, and related illnesses like heart disease, we may need to factor in information about where the fat is located. This is why we’re trying to understand what it is about adipose tissue that determines when it’s ‘full up’ and how fat ends up stored elsewhere in this situation.

AA:  Will one of the future steps of this research be to test for these MPs and TIMPs in the fat cells of people, to try and determine if they are present or absent in certain scenarios?

MF: That’s one possibility, yes. If we understand more about the MP and TIMP system, then we hope to develop tests that will be used to obtain more information about obese patients’ risk of developing type 2 diabetes – that is, to see how ‘unhealthy’ their obesity is. We would like to design a test that is simple and acceptable for patients, like a blood test, but a lot more work is needed before we can move on to that.

AA:  Okay, you’ll have to forgive me, but I can’t help picturing through all of this the little ‘adipose’ aliens from Doctor Who.  Does this happen in your lab a lot when you explain your work?

MF: I have to confess that I only recently became a Doctor Who fan (probably because I didn’t grow up in the UK!) so I had to look the Adipose aliens up – all I can say is now that I know what they are, thinking about my research is never going to be the same again! :)

AA:  Well Matthew, it has been great learning more about your research.  Thank you for taking the time to share it with all of us here at Penny University.

MF: Thanks for the opportunity to do so!

Matthew Fenech is a Research Training Fellow in Diabetes and Endocrinology, funded by the British Heart Foundation. If you’re interested in learning more about Matthew and his research, contact him via Twitter on @MattFenech83

*Today’s post title is a nod to our roots in addition to being relevant to the research featured in the post, ooh laa laa, would you look at us, being all clever and whatnot.

**Okay fine, we’ll keep ’em.