As Many Exceptions As Rules: fat

Showing posts with label fat. Show all posts

Wednesday, August 27, 2014

Let’s Chew The Fat

Biology concepts – lipid, saturation, fruit, vegetable, drupe, berry, mesocarp, cotyledon, tuber, fatty acid, triglyceride

To try and get blood from a stone dates back to the 1600’s,

meaning to try and do the impossible. It was first used in a

book by Giovanni Toriano called The Second Alphabet. As far

as the turnip goes, it may relate to a story in the Bible of Cain

and Abel making sacrifices – one a vegetable and one an animal.

The vegetable sacrifice was not as appropriate since it could

not drip blood. Now we often use the phrase for the inability of

getting someone to pay money.

Did you ever hear or use the phrase, “You can’t get blood from a stone?” Sometimes the phrase goes, “You can’t squeeze blood from a turnip.” Item one - gross. Item two, where did the phrases come from? (see picture caption) Basically, they both mean the same thing. You can’t harvest something that wasn’t there to begin with. I use it with creditors – they can’t get money from me if I don’t have any.

You can’t harvest what isn’t there, so that leads to today’s question. If plants are low fat sources of nutrition, how can we use them for cooking oils? There’s corn oil, sunflower oil, cottonseed oil, canola oil, rapeseed oil, olive oil, even coconut oil. How can such low fat organisms provide us with so much fat?

Of course every cell has fats – there are the phospholipids in the cell membrane, and phytophormones made from lipids help the cells communicate and the plant respond to stimuli. Thylakoid membranes for photosynthesis have a lipid (MGDG) that normally doesn’t form a bilayer, but does in the thylakoid. Please refer to this post to show that lipids have a role in almost every cellular activity.

Unfortunately, we don’t get oil from the whole plant, just a little part of it. And even more amazing, the part we get oil from only exists for a short time in the plant’s yearly cycle. When we say vegetable oil, we really mean fruit oil.

The fruit is the part of the plant that grows from the flower after fertilization, including the seed(s). The vegetable is all the other parts of the plant, including the flower bud before it is fertilized. Now you know the true difference between fruits and vegetables.

The fat in plants is almost always associated with its attempt to reproduce itself. Part of the fruit may be fatty, the seed of the fruit may be fatty, or even the germinating plant inside the fruit could be the source of the fat.

The upper image shows the different parts of the berry fruit

avocado. The mesocarp is the part we eat and contains the

fats. The same is true for the olives below. These have had

their seeds removed and replaced with a piece of pimento.

Maybe they thought we wouldn’t notice. No, they can’t grow

them with the pimento there already, but it might be

something Bill Blazejowski could work on, like his idea to

feed mayonnaise to the tuna in the 1982 movie, Nightshift.

Let’s start with the easiest – fruits that are high fat. The oldest is the most famous – olives. The fleshy part of the fruit, the part we eat, is called the mesocarp. In olives, up to 85% of the weight of the mesocarp is fat in the form of triglycerides. Olives have been grown for eating and pressing oil since about 6000 BCE. Olive cultivation predates written language and even teenage vampire movies.

Avocados are also pressed for oil. In locales where olives are harvested part of the year, avocados can be harvested year round, so many olive oil producer make avocado oil when the olives aren’t in season. Even though we use the mesocarp of each fruit for oil, the olive is a type of fruit called a drupe, while the avocado is actually a single-seeded berry. The avocado is just about the only berry from which we harvest edible oil.

In people with metabolic and liver function changes due to diabetes or other parts of a metabolic syndrome, it is known that the monounsaturated fatty acids in olive oil help to normalize many biochemical markers of liver function in people with metabolic syndrome. A 2014 study now expands that to avocado oil. It contains many monosaturated fatty acids, and the researchers found that it has similar positive effects on biochemical metabolic markers as compared to olive oil.

Oil palm (Elaeis guineensis or E. oleifera) fruit are also high in fat. The mesocarp is pressed to make palm oil that is used for eating and cooking, especially in Africa. The seed (kernel) can also be harvested for oil, and this is called palm kernel oil. The differences between the oil from the mesocarp and from the kernel lie in their color (the fruit oil is reddish while the kernel oil is colorless) and the percentage of saturated fats. The kernel oil is higher in saturated (no double bonds) fat.

These differences have an good side for us. Palm kernel oil esters have been shown to pass the blood brain barrier (BBB, see this post) better than other oil esters. So in a 2013 study, the palm kernel esters were combined with the antibiotic chloramphenicol. The resulting emulsion showed properties that could make it useful for treating bacterial meningitis, because more of the antibiotic could be carried across the BBB.

The mesocarp of the coconut is not edible. See the fibrous

stuff being cut away from the coconut? That’s the mesocarp,

or coir. It does have other uses though. You can make good

rope from it, or perhaps you would be more interested in some

biodegradable flower pots – all made with coir.

Another type of palm oil is also used in cooking. Coconut palm oil is pressed from the flaky coconut meat that makes german chocolate cake so irresistible. But the meat isn’t the mesocarp of the coconut fruit. You wouldn’t want to eat the mesocarp of a coconut; it’s the fibrous brown covering that has to be peeled away to get to the nut.

The coconut meat is the endosperm of the seed – the more it grows, the more of the liquid endosperm (coconut milk) turns solid. It turns solid because it is more saturated fat, and like most saturated fats it is more likely to be solid at room temperature. Coconut oil is sometimes used in place of butter.

Other “vegetable” oils come from different parts of the fruit. Sunflower oil uses the entire seed, including the embryonic plant, the endosperm and skin layers – outer (exocarp) and inner (endocarp).

Canola oil is pressed from the seeds of the canola plant. Canola is a plant bred from a type of rape plant, a member of the mustard family. Therefore, there's a really no difference between rapeseed oil and canola oil. The name "canola" was thought up in the 1970’s, using “Can” from Canada, because that is where it was developed, and “ola” as a term for oil. The word “rape” didn’t seem to help sales.

The top cartoon shows how the cotyledons can have different

fates. The brown oval cotyledons can become the first leaves in

epigeal growth, or can stay below ground in hypogeal growth.

Either way, they help the germinating plant get a good start. The

peanuts below show the cotyledons, the big parts we eat, as well

as the germinating plant. The red arrows point to the peanut

nibs; they’re actually the plumule and radicle (stems and root) of

the embryonic plant.

Drupe fruits like olives seem to make good oil. Drupes also include plants like peanuts and soybeans. However, these are different than olives. The fat from most drupes and whole seeds are found in the embryonic leaves, called cotyledons. They often serve as the first leaves of the baby plant, but they also store fat and carbohydrates for the germinating plant.

It occurs to me that the examples above are equal and opposite. On one hand, the fat of peanuts, soybeans, sunflowers, rapeseeds, and coconut serve to nourish the embryonic plant. Fat is a great idea for this function because it stores a large amount of energy in a small volume. Carbohydrates require water for storage, so they take up more room.

On the other hand, the fat of avocados, palm oil fruits and olives are enticements to other animals to eat the fruit. Why do the fruits “want” to be eaten, anthropomorphism aside? The answer - to disperse the seeds held within or on the fruits.

New plants do better when they are far enough away from the parent plant that they will not have to compete with them for resources and sunlight, especially since they will be smaller and in the shade. This is why seeds need to be dispersed. Nourishment for itself or nourishment for a predatory animal, these are two completely different functions for the fat, but both are held in the fruit.

The corn kernel is the fruit of the maize plant. There is starch

(glucose chains), gluten (protein) and the germ, which is the

germinating plant with a single cotyledon. The bottom drawing

shows the difference in constituents of different varieties of corn.

Sweet corn has more sugar, while dent corn has a higher germ to

endosperm ratio.

Given the high enough fat contents of the plant components described above, it makes sense that we could use them for oils. But what’s one of the most common “vegetable” oils used for both cooking and biodiesel? I’ll give you a hint – you probably enjoy some of this fat at the movies.

Yes, corn it is, both as your popcorn and the margarine you slather all over it. We already know that corn is amazing (see this post), but only 10% of corn is fat (dry it and 20% is fat). The sweet corn you eat is a special hybrid that contains more endosperm and less fat, but dent corn is the one used for making oil and feeding livestock. The corn kernel is mostly starch and glucose, but the embryonic plant has the fat. This is called the corn germ and is the only part used to make oil. The germ contains the cotyledon (called a scuttelum for corn) that stores fat for the germinating plant (get it? Germ = germinating plant)

Look at the bottom picture to see how small the germ of the corn kernel is. Because of this, it takes 40 bushels of dried dent corn kernels (at 56 pounds/bushel) to make 500 ml (0.85 lb) of corn oil! It must be cheap to grow corn because that isn’t a very good ratio, yet corn oil isn’t that expensive.

Tiger nut sedge looks a lot like a grass and is considered a weed

in many places. It was cultivated as far backs as 3000 years ago

in Egypt and has been used in cooking for just as long. The tubers

on top left can be eaten as a root vegetable, and are high in

monounsaturated fats. The dried tubers (bottom) can be ground

into flour or used as a spice. However, we might just start to grow

them for biodiesel. I’d line up to buy a tiger nut fueled car – that’s

really putting a tiger in your tank! (a 1960’s Esso gasoline slogan)

Even though this is a summer post, there’s no reason we can’t talk about an exception. Today, it’s sedge oil. The tiger nut sedge (Cyperus esculentus) is being considered as a viable source for biodiesel, but it's used in African cooking as well. Sedge plants reproduce in several ways. They have fruits, but they aren’t significantly high in fat. They have rhizomes and well, but we’re interested in their tubers (serves the same function as a potato).

The tubers are fairly high fat, and they’re a heck of a lot larger than corn germ. On a per plant basis, sedge produce much more oil, which will make C. esculentus a cheaper source of fuel if farmed on a global scale. In truth, since sedge oil comes from a part of the plant other than the fruit, it’s the only true “vegetable” oil we talked about today. I wonder - could we get oil from a turnip? Maybe that’s the blood we should be looking for.

Next week, we'll start a series of posts on just how bacteria get around using flagella. Can flagella be used to prove the existence of a universal designer?

Carvajal-Zarrabal O, Nolasco-Hipolito C, Aguilar-Uscanga MG, Melo Santiesteban G, Hayward-Jones PM, & Barradas-Dermitz DM (2014). Effect of dietary intake of avocado oil and olive oil on biochemical markers of liver function in sucrose-fed rats. BioMed research international, 2014 PMID: 24860825

Musa SH, Basri M, Masoumi HR, Karjiban RA, Malek EA, Basri H, & Shamsuddin AF (2013). Formulation optimization of palm kernel oil esters nanoemulsion-loaded with chloramphenicol suitable for meningitis treatment. Colloids and surfaces. B, Biointerfaces, 112, 113-9 PMID: 23974000

Wednesday, January 29, 2014

Sweet, Salt, Bitter, Sour - They Ain't The Half Of It

Biology concepts – umami, taste, flavor, gustation, glutamate, chemoreception, CD36, fat taste, water receptor, calcium

Perhaps I was a little hasty when I said umami wasn’t the name

of a new band. Apparently “Umami” is the name of a band from

Minneapolis. They are described as an electro/psych band,

whatever that is. I like it when obscure science words are used

in culture – makes me think I’m in on some secret. Umami isn’t

that obscure a word, but I used to know a band made up of

statisticians called The Outliers.

Ever heard of umami? It’s not the name of a new band, or even a bad Robin Williams movie. It’s a taste; the fifth taste that humans can sense. Umami is the taste of savory; meats and other high protein foods. And what do we have to thank for umami? Seaweed.

Until 1908, science believed that most flavors were just combinations of the four traditional tastes - sweet, salty, sour, and bitter. But don’t get the idea that taste and flavor are the same - oh no. Taste is our gustatory sense, but that isn’t the same as flavor – flavor is something bigger than taste.

You know how having a head cold makes food bland? Well, that’s because smell is a big part of flavor; you don’t smell your food when you have a cold. Food stimulates all your senses - temperature, touch, smell, what it looks like and even how it sounds as you chew it. All these things add up to flavor.

This is why chefs say you eat with your eyes first, and why they try to incorporate different textures into a single dish. They’re trying to appeal to all your senses. Therefore, eat slowly to enjoy your food more. Give all your senses time to participate. And you might just eat less, since your satisfaction will come from the total experience, not just the craving for a particular taste.

But back to the origins of umami. The Japanese had an idea that there was another taste, mostly since their traditional cuisine used so much seaweed, and this flavor couldn’t be accounted for by the other four tastes. Chemist Kikunae Ikeda wanted to identify the active molecule in seaweed, the one that gave it taste. He called it umami, from the Japanese words for delicious (umai), and taste (mi).

Ikeda’s biochemical studies led to the identification of glutamates as the molecules to which people reacted. And they aren’t just in seaweed, most living organisms contain truckloads of glutamates. When cooked, all glutamates convert to L-glutamate, the amino acid. Ikeda determined that this is what some of our gustatory (taste) receptors sense. Gustation is from Latin gustare = taste, and this is where the word gusto comes from; to taste life.

It turns out that umami taste is not produced by just L-glutamate.

Glutamate comes mostly from meat, as they are high in proteins,

but the nucleotides inosinate and guanylate also perceived as

savory tastes. Inosinates are also found in meats, but also in

seafood. Vegetables are a major source of guanylates, but so are

mushrooms – and we all know that mushrooms are fungi – right?

When you taste something, a chemical signal in the taste cells on

the tongue is converted to an electrical impulse. This is carried by

either the facial nerve or the glossophayrngeal nerve to the brain.

The most palatable form of glutamate that Ikeda could identify was monosodium glutamate (MSG), so he immediately set out to produce and sell it, starting in 1909. Made a pretty penny, he did. Now MSG is a common flavor enhancer in Japanese cooking, including soy sauce. World-class chefs are designing “U-bombs” (umami-filled dishes) to take advantage of the new official taste.

This is why identifying an umami taste receptor for L-glutamate makes sense. This is nature telling you that you need to eat protein, and by giving it a favorable neural response (it tastes good), it increases the chances that you will seek out protein sources for nutrition.

Glutamate has several functions, even beyond its role as one of twenty protein building blocks. Glutamate is the most common neurotransmitter in the central nervous system, and plays a crucial role in long-term potentiation (LTP) and learning. Glutamate is also an intermediate in synthesizing many of the molecules in glycolysis, gluconeogenesis, and the citric acid cycle. I’ve said it before and I hope it jumped into your mind just now – nature hates a unitasker.

So you sense L-glutamate through a gustatory receptor that is specific for that molecule, and the electrical impulse is converted to a specific taste – we call it savory. The cloning of the taste receptors in the late 1990’s (actually umami was the first) started people thinking about other possible tastes. Could there be a sixth taste sense – how about fats? Do we taste fats?

When in the insula of the brain, the input is sorted with other

input and interpreted as a taste. It is the perception that is

important. For the fatty acid receptors, they are receptors, they

are located in the taste cells, and they do carry information via

the same two nerves to the same part of the brain. But are they

then interpreted as a taste?

Much research has been performed in this area in the past few years and a couple of fatty acid receptors on the tongues of rodents and primates have been identified, specifically, CD36 and GPR120. But does this mean we “taste” fat? We said taste doesn't equal flavor – we should now add that sensation may not be the same as taste. Just because there are specific chemoreceptors on taste cells for different fatty acids doesn’t mean that we perceive the sensation as taste.

It has been shown that fatty acids in the oral cavity do have a threshold level for sensation, and that the fatty acid taste receptors do lead to specific changes in physiology. When subjects were given fatty acids on their tongues, they very quickly showed increased serum triglyceride levels, increased pancreatic hormone release, increased release of GI lipases (enzymes to breakdown fat) and a slowly of the GI tract (it takes more time to digest fats).

What is lacking here is a conscious perception of the discernable nature of the fatty acid (like how sugars are sweet or glutamates are savory). The 2009 studies by Mattes and colleagues controlled for the mouth feel, smell, and so forth of fats, so it was definitely the fatty acid receptor that was stimulating the responses, but no where did it say the subjects tasted something. However, his 2011 paper says that fat may very well be a basic taste.

This gives us a new way thinking about taste receptors. Taste is a type of chemoreception, but perhaps it’s only one subset of oral chemoreception. Gustatory chemoreception is a lot more than just tasting something. However, some researchers challenge this division, saying that participants do have a measurable psychophysical response when fatty acids on the tongue reach a threshold level – they do taste something.

Again I say, “nature hates a unitasker.” CD36 is the fatty receptor in

taste cells, but it also works in macrophage recognition of oxidized

fatty acids and the onset of atherosclerosis, and in the activation of

platelets by fatty acids. You can see in the cartoon that CD36 sticks

into the membrane at two places and loops out of the cell. If you

change the order of its amino acids, it’s shape will change. How well

it binds to fatty acids, or activates all those downstream signals will

also be affected. This is why people with different versions of CD36

may eat different amounts of fat. I wonder if people with poor CD36

versions also have more trouble with CD36 functions in other cells?

The CD36 glutamate receptor has been especially well studied in the past couple of years. It comes in several slightly different forms (polymorphisms – slight differences accounted for by single or few amino acid differences in the sequence of the protein), but these differences have a big effect.

When divided into groups based on which variant of CD36 they possessed, a couple of studies from 2012 (here and here) show that responses to fat and how much the subjects craved fats were different. Those who sensed fats most readily (at lowest concentrations) tended to eat less than those who needed more fat in order to trigger the responses.

The hypothesis of a 2013 review of fat taste and obesity says that those who sense less fat are more likely be tipped toward a hunger stimulating hormonal profile, while those who more readily sense the fatty acids in their food tip toward satiety (fullness). There are many hormones involved here and we could get bogged down very fast, so let’s leave it at that for now; undoubtedly someone is trying to make a diet pill based on it.

So, could there be more oral chemoreception events going on – a seventh taste? An eighth? Let’s talk very briefly about two possibilities. Maybe we can taste calcium. Yes, you could taste your Tums. A 2008 study indicated that mice can perceive calcium as a specific taste. A single 2012 study extends this to humans as well. Calcium is sensed via a certain receptor (Tas1R3), which works with other proteins to sense sweet and umami. But here, it apparently works on its own (we will talk more about the receptors in the posts to come). I need to see more research before I buy calcium taste completely.

Taste number eight - do you think you can taste water? The common argument is that you can taste what is in the water, not the water itself. How or why would you taste water; you’re 65-70% water all the time! What good is it to taste the main ingredient of life? How about this – do you sense the water by taste receptor, not just by temperature, sound, smell, or mouth feel?

There are voluntary swallows an involuntary swallows. But even

in voluntary swallows there are involuntary parts. You don’t think

about closing off your trachea with your epiglottis, it just happens.

This closing is how you keep food and liquid from ending up in

your lungs. Water in your laryngeal pharynx is one stimulus to get

you to swallow and close off the wind pipe until the possible

problem is gone.

Yep, mammals have receptors in the oral cavity that specifically sense the presence of water. In some mammals, like dogs and rabbits, using salt water inhibits the firing of the laryngeal nerve fibers connected to the water receptors; not so in cats and rats. We’ll get to why in a second.

What is the purpose for water receptors in the oral cavity (really, they are in the entrance to the throat, the laryngeal pharynx)? It may be that this is an evolutionary protection from aspirating (breathing in) liquid to the lungs. Liquid in the lung is a bad idea, since it stops gas transfer and promotes bacterial growth. If acids or other liquids that could damage the lungs or throat get in their somehow, it would definitely be better to swallow them than to breathe them in.

When you were a fetus and a very young infant, stimulation of the water receptors in your throat caused you to swallow immediately. As you aged and gained more muscular control, the reflex was replaced by coughing – this is the hypothesis of a 2001 study on the reflex. But the water receptors are still there and still aid you as a stimulus for voluntary swallowing. Whether we taste water or not, I’m glad I have the chemoreceptors.

So, the dampening of the reflex by Cl- in salt might be helpful keeping you from constantly having the urge to swallow. This leads to another point – the power of suggestion. Can you do anything right now other than think about the saliva in your mouth and whether you should be swallowing? Creepy, isn’t it.

Don’t count out the idea of water as a basic tastant (something you can taste). A 2010 study showed by monitoring brain waves that people respond to water using the same pathways as taste, and the responses look the same. And a 2012 study indicates that rats have distinct portions of the gustatory cortex of the brain for identifying both salt and water. If we can taste umami to make sure we eat enough protein, and sweet to make sure we eat enough carbohydrate, why not water to make sure we keep hydrated?

The idea here is that everything seems better if you are in love.

With love, this is a fantastic summer day in a beautiful place.

Without love, it’s just sand in a whole lot of uncomfortable places.

Same with taste, water is water – unless you're in love.

One final point that reflects just how complex taste is – did you know that being in love makes water taste sweeter? Participants in a December 2013 experiment were asked to think or write about love, hate, or jealousy. Then they were asked to describe the taste of a new product (really just distilled water). Those who wrote or thought about love rated the water to be sweeter than those who contemplated hate or jealousy.

It seems that the brain pathways for rewarding feelings in love and in consuming sweet are the same. You can’t discern between the two, and one can stimulate the other. So when you say you love eating sweets, maybe you really do!

Next week, we can go further into taste. Do people who are supertasters taste good or taste well?

Newman L, Haryono R, & Keast R (2013). Functionality of fatty acid chemoreception: a potential factor in the development of obesity? Nutrients, 5 (4), 1287-300 PMID: 23595136

Pepino MY, Love-Gregory L, Klein S, & Abumrad NA (2012). The fatty acid translocase gene CD36 and lingual lipase influence oral sensitivity to fat in obese subjects. Journal of lipid research, 53 (3), 561-6 PMID: 22210925

Keller KL, Liang LC, Sakimura J, May D, van Belle C, Breen C, Driggin E, Tepper BJ, Lanzano PC, Deng L, & Chung WK (2012). Common variants in the CD36 gene are associated with oral fat perception, fat preferences, and obesity in African Americans. Obesity (Silver Spring, Md.), 20 (5), 1066-73 PMID: 22240721

Chan KQ, Tong EM, Tan DH, & Koh AH (2013). What do love and jealousy taste like? Emotion (Washington, D.C.), 13 (6), 1142-9 PMID: 24040883

MacDonald CJ, Meck WH, & Simon SA (2012). Distinct neural ensembles in the rat gustatory cortex encode salt and water tastes. The Journal of physiology, 590 (Pt 13), 3169-84 PMID: 22570382

For more information or classroom activities, see:

Umami –

http://www.macheesmo.com/2012/01/what-is-umami/

http://www.foodrepublic.com/2013/07/11/food-scientist-explains-umami-molecular-level-now

http://bitesizedbiology.tumblr.com/post/55028228406/understanding-umami-imagine-taking-a-bite-of-your

http://www.buedelmeatup.com/2012/12/11/umami-the-fifth-primary-taste/

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

http://www.youtube.com/watch?v=W2xPOZPlxo4

http://www.nature.com/nature/journal/v457/n7226/full/457160a.html

http://chemse.oxfordjournals.org/content/27/9/843.full

Fat taste –

http://www.washingtonpost.com/national/health-science/fat-might-be-the-sixth-basic-taste/2012/06/04/gJQAt218DV_story.html

http://recipes.howstuffworks.com/why-does-fat-taste-so-good.htm

http://www.foodnavigator-usa.com/R-D/Fatty-taste-receptor-may-explain-fatty-food-preference-Study

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCkQFjAA&url=http%3A%2F%2Fwww.9healthfair.org%2FContent%2Ffile%2FSugar%2520Salt%2520and%2520Fat.pdf&ei=GdnWUq2eMILQyAH_9IHAAQ&usg=AFQjCNFS5vk34it-6dSFErpK7tiwZMnFYA&sig2=cMULFKdRRH8UkovtgD4aYg

http://www.sciencedaily.com/releases/2001/12/011204073223.htm

Water receptor –

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967336/

http://link.springer.com/article/10.1007/s00221-013-3641-y

http://ajpgi.physiology.org/content/301/2/G197

http://ajpgi.physiology.org/content/270/2/G347

Wednesday, December 4, 2013

The Skinny On Fat

Biology concepts – lipids, fatty acid, saturated fat, trans fat, interesterification, adipose tissue, lipodystrophy, LDL and HDL

This is Lizzie Velasquez, a 24 year old with a genetic

form of lipodystrophy. She must consume 5000-

8000 calories and eat 80 times each day just to survive.

Her condition is called neonatal progeroid syndrome,

which includes premature aging and an oversized head

along with the lipodystrophy. She has dealt with more

than any person should have to, and now is a

motivational speaker – "it’s going to get better" is her

theme. Her second book, Be Beautiful, Be You is a

must read. The picture is from one of her public talks.

Most of us worry about gaining weight. We would love to be skinnier, lighter, trimmer, svelter (a new word?). But what if you had the opposite problem – you couldn’t gain any weight, no matter how much you ate?

There is a group of disorders known as the lipodystrophies (lipo = fat, dys = bad, and trophy = nourishment) in which afflicted people can't store any fat. Their stories tell us that being skinny is no blessing.

Lipodystrophies can be congenital (con = with, genitus = to beget), so they are present from conception, or they can be acquired. In congenital cases, the genetic mutation sometimes has little to do with fat, sometimes it does. There are four known mutations in four different proteins that can all lead to a lipodystrophy.

People with a congenital lipodystrophy tend to develop type II diabetes. They also get arthritis and other disorders. Some mutations also carry higher risks of mental retardation and most increase the risk of cardiac disease and cirrhosis of the liver. These can kill you.

Acquired forms often result from drug treatment. In HIV retroviral treatment, there can by lipodystrophy and lipoatrophy – which is loss of fat from one particular anatomic location, usually the face. On the other hand, visceral fat (fat around the internal organs) is increased during anti-HIV treatment. It matters, since visceral fat is associated with more heart and liver disease.

Lipoatrophy refers to the loss of fat in a particular area of the

body. On the left is the facial atrophy seen in patients on anti-

viral therapy in HIV infection. On the right is a specific

lipoatrophy surrounding an insulin injection sight for diabetes.

A 2013 study sought to determine why the opposite things happen with fat in different places. They tracked different markers in each location and found that mitochondrial changes were the same in visceral adipose tissue (VAT) and subdermal adipose tissue (SAT). But the signals to build fat decreased only in SAT. Most telling, inflammatory signals were much greater in SAT than in VAT; it may be that less inflammation leads to less fat wasting. Strange that fat would be linked to inflammation – or maybe not - keep reading.

Fat may be considered evil, but it serves a purpose. The problems that lipodystrophy patients encounter underline that fat is a necessary tissue for animals. Problems arise when you accumulate too much of it, either under your skin, around your organs, or in your blood. If you don’t use the calories you take in for energy, your body will store them for later.

Chemically, a fat is made up of three fatty acids (see below) attached to a 3-carbon glycerol molecule. In adipose tissue (from latin aipem = fat) and subcutaneous fat, these triglycerides, also called triacylglycerols (tri = 3, glycer = glycerol, and acyl = acid) are stored until they are released to the blood stream as fatty acids alone. The fatty acids can then be broken down and used to generate ATP in the cells.

Fats are a much more efficient storage form of energy as compared to glucose or glycogen. There is 4.5 x more energy in fat as compared to the same mass of glycogen or glucose. In addition, since fats are hydrophobic (hydro = water, and phobic = fearing), they can be stored without water. These two factors mean that a lot of energy can be stored in a little space.

A fat molecule is really a triglyceride. The right structure is a

typical triglyceride with three fatty acids in black connected

to the bluish glycerol. By ester bonds in dark red. A trans

double bond is shown in green. On the right is the partial

hydrogenation process that converts a polyunsaturated fat

into a trans fat. Usually there is a mix of products, with some

cis bonds being converted to trans bonds.

Glucose first gets stored as glycogen, but we make only a certain amount of glycogen. Usually a human has about one lazy day’s worth of glycogen. Energy beyond that gets stored as fat, and that’s a good thing. Imagine how large we would all be if we all our energy reserves were in the form of glycogen + water. A normal human adult male would weigh an extra 110 pounds (50 kg)!

A fatty acid is a chain of carbons with a carboxyl group (HO-C=O) on one end. If the chain of carbons contains only single bonds, then the fatty acid is called saturated. If there is one double bond between carbons, then it is an unsaturated fatty acid, and if there are two or more double bonds (unsaturations), then it is a polyunsaturated fatty acid.

The same terminology is used for triglycerides (fats) made from the fatty acids. A fat with only saturated fatty acids is a saturated fat. The double bond type also makes a difference for the fatty acid and fat. If the bond is in one configuration, it is called cis, and it creates a bend in the chain. If the double bond is in the other configuration, then it is called trans, and it is much straighter, like a saturated fatty acid.

You have heard of the benefits of polyunsaturated fats as opposed to saturated fats, and of the evils of trans-fats. Saturated fats tend to produce bad results in the blood stream. Their breakdown results in more acetates which stimulate cholesterol production. Also, saturated fats tend to clump together and form blockages in vessels. This leads to atherosclerosis and can kill you.

The left cartoon shows the buildup of plaque over time in

atherosclerosis. It takes along time, but we all seem to be

working hard to make it happen. The right image is a

photomicrograph showing the blockage in a large coronary

artery. Think the amount of blood getting through is enough

to nourish your heart? Think it’s going to have a happy ending?

However, saturated fats are good at promoting liver and lung health, so some saturated fat in your diet is not a bad thing. Trans-fats, on the other hand, are harder to discuss. They can be made in a factory by removing some double bonds from polyunsaturated fats by partial hydrogenation. They also occur naturally, but are very rare compared to cis fats, so they don’t usually cause a problem.

The vast majority of trans fats we eat are industrially made. The trans double bonds are created in the hydrogenation process (adding hydrogens to reduce the number of double bonds). Some cis- double bonds become trans- double bonds during the process.

Industry likes the saturated and trans-fats because they tend to be more solid at room temperature (higher melting temperatures). Saturated and trans-fats have more hydrogens (see picture above). The kink in trans-fats also increases the melting temperature.

The hydrogens and kinks lead to more interactions between the different molecules – they hold on to one another more tightly. Melting is basically making the different molecules separate by adding energy, so the added hydrogens have the end result of raising the melting temperature. This is good for making things like margarine.

Unfortunately, trans-fats tend to increase low-density lipoprotein (LDL) production; these contribute greatly to artery clogging and heart disease. The blocking of arteries is bad enough, but if they occur in the brain, or if part of a plaque breaks off, travels to the brain and blocks a vessel – that’s a stroke. There’s not much that’s worse than a stroke.

Saturated fats also raise the levels of LDL’s - so why are trans-fats worse for you than saturated fats? The levels of LDLs are only one aspect in disease promotion, the level of the good-for-you HDLs (high density lipoproteins) is just as important. It's the ratio of LDL:HDL that matters.

In the space of the vessel are some large cells with very

light cytoplasm that looks like Swiss cheese. There are

many small clear droplets and some larger ones. These

are fat droplets and give the cells their name – foam cells.

You can see that some have more than one nucleus. Two

diseased macrophages will often merge into

multinucleate giant cells.

When you eat saturated fats, both the LDL and the HDL levels increase, so the ratio stays generally the same. With trans-fats, the LDL production goes up but the HDL level stays the same or decreases. This leads to a bad ratio and disease progression.

The next question then is how do HDLs help prevent disease caused by LDLs? LDLs supply cholesterol to the cells that need it – and that’s all your cells (more on this next week). But if there is too much LDL, then they start to accumulate in the vessels and can form things like foam cells.

Foam cells are tissue macrophages located in/on the vessel walls. The job of macrophages is to eat things, so these macrophages eat up the extra LDLs in the area - but they don’t break them down. They build up and start to look like foam inside the cell. Unfortunately, the macrophages then become part of the problem; as they accumulate they form fat streaks in the vessel wall. This is the beginning of plaque formation and atherosclerosis.

A 2005 review looked at how HDLs are health promoting. It turns out that they steal cholesterol from LDLs, but they don’t promote the formation of foam cells and plaques because of their different structure. Therefore, having more HDLs will rescue more cholesterol from LDLs and transport it to the liver for eventual destruction.

The top cartoon shows how HDL help get rid cholesterol

after it has been phagocytosed by a macrophage foam cell.

A pre-HDL interacts with receptors on the macrophage

which then transfer cholesterol to the HDL. This is taken to

the liver where it is broken down and reused for bile

production. This is called reverse cholesterol transport. The

bottom image shows the functions of HDL, even beyond its

ability to negate the unhealthy effects of LDLs.

By stealing the cholesterol from LDL, HDLs also stop many mechanisms that can lead to vessel blocking, like the stimulation of vessel inflammation by LDLs, the formation of clots in the vessels (HDLs are anti-thrombotic, a thrombus is a clot), and by preventing the oxidation of LDLs.

Oxidation of LDLs leads to oxygen radicals can damage vessel cells and promote plaque formation. But HDL complexes include an enzyme called paraoxonase, which prevents the oxidation of closely associated LDL molecules. Preventing oxidation also reduced the production of pro-inflammatory molecules in the vessel wall and decreased the recruitment of some inflammatory cell to the area. Hurrah for HDL!

But wait – of course there’s an exception. HDLs from patients with existing diseases, like coronary artery disease (CAD) or chronic kidney dysfunction (CKD) actually contribute to plaque formation rather than prevent it! A 2013 review talked about how HDLs from CAD patients limit the anti-inflammatory and repair processes in the vessels cells, and in CKD patients promote inflammation and raise blood pressure. I guess the best way to prevent atherosclerosis is to not develop atherosclerosis.

Overall, you want to reduce fat intake, but especially trans-fats and saturated fats. Food labels are now required to show how much trans fat is in the product, but the manufacturers are getting around the regulation. They combine different fatty acids in a fat and they call them interestrified fats. Partial hydrogenation is still a major factor, but they aren’t called trans-fats. This allows them to keep it below the FDA radar. Interesterified fats don’t exist in nature – that should tell us all we need to know.

What we need is a way to partially hydrogenate the polyunsaturated fats that does not create trans-fats – you work on that while I butter my bagel. Next week we can look at more aspects of fats, and how they are different from the other lipids.

Gallego-Escuredo JM, Villarroya J, Domingo P, Targarona EM, Alegre M, Domingo JC, Villarroya F, & Giralt M (2013). Differentially Altered Molecular Signature of Visceral Adipose Tissue in HIV-1-Associated Lipodystrophy. Journal of acquired immune deficiency syndromes (1999), 64 (2), 142-8 PMID: 23714743

Xu S, Liu Z, & Liu P (2013). HDL cholesterol in cardiovascular diseases: The good, the bad, and the ugly? International journal of cardiology, 168 (4), 3157-9 PMID: 23962777

Barter, P. (2005). The role of HDL-cholesterol in preventing atherosclerotic disease. , 7(Suppl F), F4-F8. European heart Journal, 7 DOI: 10.1093/eurheartj/sui036

For more information or classroom activities, see:

Trans fats –

http://www.mayoclinic.com/health/trans-fat/CL00032

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCoQFjAA&url=http%3A%2F%2Fwww.bellinstitute.com%2FDisplayResource.aspx%3FID%3D466&ei=b2hoUoDRJOb4yQGupIHAAg&usg=AFQjCNGD6kQGhpmZww0_ozraek5mgGPkVw&sig2=q8qehRUhNomxEp73WrI0DA&bvm=bv.55123115,d.eW0

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CDAQFjAB&url=http%3A%2F%2Fnfsmi-web01.nfsmi.olemiss.edu%2FDocumentDownload.aspx%3Fid%3D2494&ei=b2hoUoDRJOb4yQGupIHAAg&usg=AFQjCNFOoBeS_l85BN1JdxRW44Oeq7_YUA&sig2=1drqYVxeKTILlnhbtU-jrw&bvm=bv.55123115,d.eW0

http://www.pbs.org/wgbh/nova/education/activities/3401_01_nsn.html

http://www.uen.org/Lessonplan/preview.cgi?LPid=1265

http://www.bantransfats.com/mcdonalds.html

http://howtosmile.org/record/4406

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=17&ved=0CFIQFjAGOAo&url=http%3A%2F%2Fllaa.org%2Fsites%2Fdefault%2Ffiles%2FTrans%2520Fat%2520Activity%2520Outline.pdf&ei=KWloUvTMK8TgyQH__oDQAw&usg=AFQjCNGmgcQon8-2bYF5FRmIo5V9_4nrtg&sig2=moOFRCVVJHrdsX_RxIx2BA&bvm=bv.55123115,d.eW0

http://www.slideshare.net/muskokee/transfats-biology-of-food-safety-class

interesterification –