on Lipid Molecules
Guest: Dr. Yusuf Hannun – Biochemistry & Molecular
Host: Dr. Linda Austin – Psychiatry
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
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?
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.
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.
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
Dr. Linda Austin: Like
Vioxx, I think, is that right?
Dr. Yusuf Hannun: Yes,
Dr. Linda Austin: Targets
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
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
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