Hello, I'm Bob Farese, Jr.
And I'm Toby Walther.
And we run a joint laboratory
at the Harvard School of Public Health
and Harvard Medical School,
and the Howard Hughes Medical Institute in Boston, Massachusetts.
And today, we'll tell you about a fascinating organelle
called the lipid droplet.
As you all know, life is defined
by an open equilibrium of energy
that flows through the biological system
and allows the system to maintain its structure
and to perform work.
But, of course, energy availability
and the need to expend energy
varies greatly over time.
And as a consequence,
pretty much all biological systems
have evolved mechanisms to temporarily store metabolic energy.
And they do so primarily, as you can see on the slide,
in the form of lipids,
that contain most of the metabolic stores in a human,
for instance.
The major lipid that most organisms store energy in
is in triacylglycerols or triglycerides.
And they are the universal currency of energy storage
because, one, they're energy dense;
two, they are highly reduced and available for oxidation;
and three, they don't require water for their storage.
In fact, as we all know,
oil and water don't mix,
so oils are partitioned separately from water,
as you can see in the movie on your left.
As a consequence of these somewhat unique properties,
lipid droplets were about the first organelles
to be discovered.
Because oil and water diffract light,
Richard Altmann was able to observe lipid droplets,
in this case, in frog liver cells,
where you can see the densely stained lipid droplets.
This is a really interesting book to look at,
by Richard Altmann.
He's also the person who discovered by bioblasts,
later termed mitochondria,
and termed... and coined the term nucleic acid or nucleinsäure.
So, lipid droplets are ubiquitous organelles,
but they're also highly unusual organelles.
As you can see in the electron micrograph
on the left from a hepatoma cell,
lipid droplets are bounded by a monolayer
instead of a bilayer,
which is typically what organelles
such as the endoplasmic reticulum mitochondria, or the nucleus,
which are also shown in the micrograph, have.
On the right is a schematic of lipid droplets
that shows their composition.
So, these organelles have a neutral lipid core,
which typically is sterol esters
or triglycerides or sometimes waxes,
wax esters.
And those neutral lipids are bounded by a phospholipid monolayer.
And the phospholipid monolayer is decorated
by specific proteins that number in the 10s to 100s
and are typically involved in lipid metabolism.
Now, the presence of lipid droplets
converts cells to emulsions.
An emulsion is a system where more than one phase
is present at the same time.
And in this case, the cell becomes an emulsion
because lipid droplets form a dispersed phase
in the continuous phase of the cytosol.
Because such a system is always metastable,
and there's a tendency for both phases
to just separate out from each other,
these is emulsifier or surfactant required
to lower the surface tension
and prevent all the droplets from coalescing together.
Now, as I mentioned, lipid droplets are ubiquitous.
They're found in almost all eukaryotic cells,
and they're even found in some prokaryotes.
These are some examples of lipid droplets
in different cell types,
and here we're visualizing lipid droplets
with a neutral lipid fluorescent dye,
such as BODIPY.
And as you can see,
there are some bacteria that have lipid droplets.
In this case, we're showing Rhodococcus,
but also mycobacteria have lipid droplets.
And also shown here are yeast cells,
with their typical 4-8 numbers of lipid droplets,
fly cells with lipid droplets,
or mammalian cells with lipid droplets.
In multicellular organisms,
often lipid storage is separated into a dedicated tissue.
For instance, in humans,
adipose tissue stores most of the triacylglycerol
and neutral lipid for energy stores.
Importantly, though,
pretty much all other cells in the human body
have the capacity to make lipid droplets
and store energy temporarily.
For instance, after a meal, the intestine stores, temporarily,
lipids and lipid droplets,
here shown in blue.
The liver takes up lipids from circulation
and from adipose tissue, actually,
and temporarily stores those lipids,
now shown in red here.
These are some of the most metabolically active organs.
It's also important to remember, for instance,
that the heart runs predominantly on fatty acids as a fuel,
and in some instances lipid droplets
become very prevalent, when, for instance,
heart function is compromised.
There are also a number of really fascinating biology problems
and processes that involve lipid droplets,
particularly the secretion of lipid droplets
in an unconventional mechanism,
in the mammary epithelium to make milk,
which of course has a lot of fat in it.
Now, as Toby mentioned, lipid droplets
are part of normal metabolism
and, in particular, lipid and triglyceride metabolism.
But a proper balance of lipid droplets
in cells and tissues is required,
because, as we all know,
basically obesity constitutes a state
where there's an excess abundance of lipid droplets
in the organism.
And conversely, lipodystrophy, or the lack of fat,
is a situation in which lipid droplets are scarce or absent.
And importantly, both of these conditions
are associated with insulin resistance
and diabetes and illness.
Now, the molecular mechanisms
that link the overaccumulation of lipids to disease
are still under intense investigation.
Generally, it is thought that excess lipids
flow over into tissues
where they're normally not very abundant.
This includes, for instance, the liver, muscle,
the pancreas, or the heart.
In those cases, it is thought that the lipids
-- the excess lipids --
interfere either directly or indirectly
with the normal physiological function of the tissue,
and this leads, then, to a form of toxicity.
This has led to a term known as lipotoxicity,
first coined by Roger Unger in the '80s.
In some cases, as Bob just mentioned,
this then results as an end effect in diabetes,
for instance.
In other cases, cardiovascular diseases,
such as cardiomyopathy and atherosclerosis,
are the consequence of overaccumulation of lipids and lipotoxicity.
Now, lipid droplets and triglyceride storage in lipid droplets
are also important in other processes --
for example, they have industrial importance.
So, for example, in agriculture,
seed oil production is a very important
aspect of lipid droplet storage,
and one that is...
that is under intense investigation for optimizing oil production.
Similarly, for renewable energy,
biofuel production essentially relies on the enhanced production
of triglyceride storage in lipid droplets.
As we told you, lipids and water don't mix,
and the formation of droplets
is a biophysical process.
However, cells have evolved
very complicated machinery
to synthesize lipids,
organize the formation of lipid droplets in specific sites,
and to regulate that process.
This is an intense area of investigation,
and if you want to learn more about it,
please stay tuned.