Research on Lipid Molecules

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Research on Lipid Molecules




Guest:   Dr. Yusuf Hannun – Biochemistry & Molecular Biology

Host:  Dr. Linda Austin – Psychiatry


Dr. Linda Austin:  I’m Dr. Linda Austin.  I’m interviewing Dr. Yusuf Hannun who is Professor of Biochemistry and has many other titles, including Associate Director of Research at Hollings Cancer Center here at the Medical University of South Carolina.  Dr. Hannun, in this podcast, I want to hear about your research which I know is really technical, but maybe we could go through it slowly and if there are big words that come up, I may ask you about those.  What do you do?


Dr. Yusuf Hannun:  We study lipid metabolism and its mechanisms and function, and maybe I should explain that.  Lipid molecules are probably known to the public as fat molecules and, probably, the public thinks of them mostly as what gives you calories and problems with obesity, and what have you.  But what we have learned, and it has taken several decades to come to this point, is that many lipid molecules within the cell, within individual cells in our tissues and organs, can play important regulatory roles in the cell, meaning, some lipid molecules work to communicate information between cells.  Some lipid molecules function to communicate information within the cell, maybe, perhaps between the different subcompartments of the cell or in response to specific changes in the cell. 


So, it becomes important to understand who are these lipid molecules, how are they made, what regulates them and, in turn, what do they do, how do they do it and how do they contribute to cell function?  Why is that important?  It is important because many of these lipid molecules play important roles in normal cell function.  And when there are disruptions in these normal mechanisms, one can get serious problems. 


Again, perhaps, some of the best known lipid molecules, to the public, are eicosanoids and prostaglandins.  They’re probably not known to the public as such, but they’re known indirectly because these are the targets of the COX inhibitors, the cyclooxygenase inhibitors that have been used in arthritis, primarily, and have problems with cardiovascular problems.


Dr. Linda Austin:  Like Vioxx, I think, is that right?


Dr. Yusuf Hannun:  Yes, correct, Vioxx.


Dr. Linda Austin:  Targets those, yes?


Dr. Yusuf Hannun:  Yes, targets that enzyme.


We work on a number another class of lipids called the sphingolipids.  This is one of four main classes of lipids, or three classes, depending on how you classify lipids, but one of the major ones, and it has a number of molecules that, again, play very important roles.  Some of those roles are also in inflammation, just like those [lipids] that are targeted by COX inhibitors.  Others, in our interest, are that they play a role in cancer, evolution of cancer, and as, possibly, mechanisms of resistance to cancer.  


By understanding how these happen, we can then hopefully tilt the balance so that cancer cells become more sensitive to therapeutic treatment.  Some of these lipid molecules also, we are learning, play important roles in diabetes and what’s called the metabolic syndrome.  They accumulate, for example, a molecule called ceramite, which we work on.  It accumulates in response to a load of fatty acids, to an increase of fat in the diet.  And they may contribute to some of the problems that arise from increased fat in the diet as well as increased weight and obesity, in terms of dysfunction of the fat tissue, dysfunction of the liver and dysfunction of the pancreas. 


So, the lipids we work on are emerging to be very important in a variety of human conditions that are of relevance to the public at large.  And what we try to do is provide the fundamental knowledge about these molecules, how they’re made, what makes them, what do they do, how do they affect those functions, because that’s how we then can understand them and become more rationally directed in dealing with them in their respective diseases.


Dr. Linda Austin:  You know, I think the public is becoming a lot more interested in the molecules of nutrition and how they play a role.  I’m thinking, for example, of fish oil, which has become kind of standard fare, I guess, in the medicine cabinets of many people.  Are there other examples of commonly known lipids or fatty acids that the public is becoming interested in, in terms of what they can do to boost immune function or play a role?


Dr. Yusuf Hannun:  Some of the molecules we’re interested in are, for example, present in milk and dairy products, and they get metabolized in the intestines, so they do affect the host body responses and body functions.  And that, again, tells us what we kind of know in a general way, that there is an interaction between what the body receives, in terms of food, small molecules, lipid molecules, and how the body functions.  But I don’t think we know, very well, the specifics of those mechanisms, even with fish oil.  We’re still probing, I think, the surface of how fish oils, what are called Omega-3-hydroxy fatty acids, change the normal function of the cell or may attenuate things such as inflammation or some functions of cells that could be important for heart disease, for example.  We’re scratching the surface on that.  There’s a lot of research to be done, not just on fish oils, but milk fats, other lipid molecules that we work on, and other lipid molecules that we don’t work on.  But, they are present.  Lipid molecules are present in plants.  They’re present in animal sources of food.  They’re all over.


Dr. Linda Austin:  Now, I’m having to dig back many years to my biochemistry course in medical school, which was quite awhile ago, but what I’m remembering is that genes code for proteins, which, of course, are a very different category, which, though, can be enzymes, and that, surely, affects fatty acid metabolism.  So, I’m wondering, as you’re talking about these fats, these lipids, that you investigate, to what degree are they controlled by, indirectly at least, or downstreamed by genes versus come about by virtue of diet?


Dr. Yusuf Hannun:  They’re definitely controlled both ways.  Any individual cell in the body has a large array of enzymes, as you mentioned.  These are proteins made by genes.  Many of these enzymes work specifically on lipid molecules.  They can turn lipid A to lipid B, and another enzyme will turn lipid B to C, C to D, etc.  That’s how the body makes its own cholesterol.  That’s how the body makes its own eicosanoids, you know, the targets for the COX inhibitors.  That’s how the body makes the sphingolipids we work on.  And the body, also, can receive, as we mentioned, lipids from the diet.  But, also, in a more complex way, it’s all interchangeable.  I mean, if someone eats sugar, an excess of sugar, it will get metabolized into fat, and that’s how it gets stored, primarily as fat.


So, there’s a huge interchange between, basically, various carbon sources, whether it’s amino acids from proteins or sugars, or fats.  They can be interchangeable in the body.  So, it’s a complex area of biochemistry to be able to follow these molecules as they interchange or transmutate, if you will.  But the body, to go back to your question, has a lot of enzymes to deal with it, as well as other proteins that deal with the transport of these lipids and with changing them from one to the other, to the other. 


Dr. Linda Austin:  Dr. Hannun, thank you so much for talking with us today.


Dr. Yusuf Hannun:  Thank you.


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