Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we will assume that you are happy to receive all cookies and you will not see this message again. Click 'Find out more' for information on how to change your cookie settings.

Following the online release of “The molecular cell biology, metabolism and physiological functions of lipid droplets”, a special issue of Seminars in Cell and Developmental Biology, Associate Professor Robin Klemm gave a special interview outlining the significance of lipid droplet research and how he approached putting together the issue, together with an introduction to how his own work fits into this vibrant newly emerged field and why he came to DPAG.

Why are lipid droplets so important?

This is an interesting question because lipid droplets are quite ubiquitous which means they are present in literally all our cells and they take over such versatile functions. They are central in fat metabolism, and as a matter of fact in metabolic homeostasis in general, so they are really a metabolic hub. At the same time, they are also really important for cell biological functions that on the face of it would not be linked with lipid biology. It’s a really interesting aspect to study that has importance on a basic science level and it’s also medically relevant.

When you came to approach editing this review, were there any particular questions that you were looking to address? And how did you approach achieving that?

This was a really interesting opportunity for me because I am relatively new in this field and I have a very basic science approach to the whole problem. I tried to mobilise the community I am in touch with to discuss the problem of lipid droplet-biology and metabolism. So, I designed this issue with the idea in mind of bringing together basic cell biology, which means the molecular mechanisms that underlie the formation of pathways and cellular structures, and also integrate this with the physiological function of the cellular aspects. This review issue has ten independent contributions and they really bridge that spectrum of topics; from the molecular, or even sub-molecular, perspective to the physiological regulation, the endocrinological regulation, of metabolism. And lipid droplets are central to all of these aspects. I hope that it inspires not only molecular cell biologists, but also physiologists are increasingly getting interested in the molecular aspects, because I think this is really the way forward in treating, and also understanding, metabolic issues, which is really an increasing problem in societies. And not only in the industrialised world, but also in the developing world, we really have an issue with metabolic disorders and lipid metabolism is really not enough understood to tackle this issue effectively.

What would you say has been the most important development in research into lipid droplets and how has this advanced our understanding of various human physiological processes?

It’s a very interesting point and it has also a historical perspective. It’s also very interesting to ask this in Oxford because metabolism was classically here a mainstay of science, especially the former biochemistry setup was very metabolically orientated. Having said this, metabolism and especially lipid metabolism was really one of the oldest fields in molecular cell biology or molecular physiology or medical physiology as it was often called back then. And somehow, we forgot all of this because molecular cell biology shifted into a different direction, and now we have to bring this together. The most important development was the recognition of the lipid droplet as an organelle, which sounds maybe really strange because why would an organelle not be recognised, but people really did not think that it was an independent organelle with molecular machinery regulating its function integrating it into other cellular processes. It was for literally a hundred years considered a very inert passive organelle floating around in a cell. I think that this has changed over the last 25 maybe 30 years at most. This was really important and it will be medically extremely relevant.

Where does your own research fit into this rapidly advancing field and what drew you to it?

I’m a cell biologist by training, a biochemist, and I think this is a really interesting perspective to contribute to physiological metabolism. I’m really excited to be here in a physiology department and get inspired by a world that I am yet not so familiar with, and I can contribute the molecular cell biology perspective to it. That is, how do organelles that you find in the cell interact with the lipid droplet, literally physically and also then functionally, what is the molecular machinery underlying these processes? And what is really defective in diseases that are related to defects in lipid metabolism or metabolic disorders? This is something that I’m really excited about; joining the classical field of metabolism with cell biology. This is exactly what drew me into it and I’m really fascinated by it.

You are focusing in particular on adipocytes – could you walk me through their particular relevance and why you chose to focus on them?

It was again motivated by a historical perspective. When the electron microscope was invented people really expanded our view into the ultrastructural level of cell biology, and the adipocyte was investigated a lot. What is really interesting is during the development of an adipocyte, the lipid droplet, which is of course the professional organelle for fat storage in adipocytes, is in physical contact with almost all the other organelles in the cell. When I studied organelle morphology as a postdoc and really basic biochemical processes, I was convinced there is molecular machinery that is not completely understood organising this physical and spatial and functional interplay between all these organelles in the cell and the lipid droplet. So, the lipid droplet in an adipocyte is bound to become extremely huge, that’s the function of an adipocyte lipid droplet for fat storage, and we have at the same time, through that process of lipid droplet growth, a very good readout for studying these interactions on a functional level. That was my motivation to go into it, and also the adipocyte is a classical cell type, which is really important for our whole body metabolic health and fat storage. It is not really clear what is molecularly defective when people turn obese or insulin-resistant and that is really my focus. I want to understand these connections between defective cell biology and physiology on a molecular level.

In understanding these areas and consequently advancing our knowledge of fat cell biology, what would be your key research goal?

Mainly really two goals. The first one is more of a basic science question related to the lipid droplets in adipocytes, because during the development or differentiation of an adipocyte, the adipocyte lipid droplet is really made de novo. So, we can follow the birth of an organelle, and to follow this on a molecular level, understand the molecular machinery that brings about this new organelle and how it grows out of another organelle, is really fascinating.  At the same time, the growth of the lipid droplet and the fat storage in the lipid droplet is really related to a lot of physiological aspects in the human body. This has of course clinical relevance. The most important point that I’m interested in is the development of insulin-resistance, which is the core etiological signature of type 2 diabetes, and it is not exactly clear how the disease emerges. It’s now a theory or thesis in the field that I try to test, and that is that metabolic defects in adipose tissue precede insulin-resistance in muscle and heart tissue. It was previously thought that it is the other way round; that insulin-resistance is really the cause for defects in fat biology. It might be not that clear, and that is really my focus. So, I’m really interested in understanding the contribution of various aspects of fat metabolism to the development of type 2 diabetes and obesity.

Why did you decide to conduct your research at DPAG?

This is a fantastic opportunity to make a dream of mine come true and that is joining a classical physiology environment and contributing the perspective of a molecular cell biologist and a biochemical perspective to understanding the function of a certain cell type, the adipocyte. I also really believe that contributing the molecular view is the basis on which we can make significant headway and improve our understanding of the molecular reasons for the metabolic diseases that we face. In particular, developing new therapeutic strategies might really be inspired by a molecular perspective in understanding the basic machinery that builds up fat storage organelles and how this interplays with the physiological counterparts in other cell types.