Your new afternoon snacks?

It’s 3PM and you’re at your desk fighting determinedly to keep your eyes open. You think maybe some candy or soda could give you the sugar rush you need to get through the last few hours of the work day, so you head to the vending to get some — STOP! Wait a minute. You might want to read this post first before you snag those M&M’s; new research shows that protein might do a better job of keeping you awake, and burning your calories, too.

As someone who’s happiest with meat at every meal, I say: pass me the jerky.

Everyone’s familiar with the concept of a sugar rush: you eat a ton of sweet stuff, you get a huge rush of energy and hyperactivity, and then you “crash” and feel more tired than you did before eating the sweets. That said, it’s almost logical to think that sugar would stimulate cells that help keep us awake. What cells are those? They are neurons called orexin cells, which secrete a stimulant into the brain to help keep us awake and burn calories. In fact, these neurons are less active in obese people and narcoleptics.

Researchers in the U.K. set out to find what makes these drowsiness-busting, calorie-burning neurons tick. They labeled the orexin neurons in mouse brains using genetically-directed fluorescence; this way, they could introduce different types of nutrients and look at their effects on the activity of only the orexin neurons. Interestingly, glucose was found to inhibit these cells, which might explain after-meal sleepiness when the sugar from your food gets into your blood and then to your brain. In a recent follow-up publication, this same group found that dietary amino acids, like the ones found in egg whites, stimulated orexin neurons — these amino acids even reversed the inhibitory effect of glucose.

In other words, and to vastly oversimplify, sugar might contribute to making you sleepy and stout, while protein could help to keep you lively and lean. These findings could to explain previously mystifying studies in which protein meals made people more alert than carbohydrate meals. Additionally, these results could be especially important for altering the dietary compositions of people with disorders like obesity, insomnia, and narcolepsy.

So, if you swap out a candy bar for a protein bar with the same number of calories, the protein might tell your body to burn more of those calories, and you’ll get through your day with fewer yawns. Sounds like a good trade to me.

Stay nerdy.

Burdakov D, Gerasimenko O, & Verkhratsky A (2005). Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ. The Journal of neuroscience : the official journal of the Society for Neuroscience, 25 (9), 2429-33 PMID: 15745970

Karnani MM, Apergis-Schoute J, Adamantidis A, Jensen LT, de Lecea L, Fugger L, & Burdakov D (2011). Activation of central orexin/hypocretin neurons by dietary amino acids. Neuron, 72 (4), 616-29 PMID: 22099463

SNL

I was exponentially more surprised when the same thing happened again, less than two minutes later. Yes, Seth was making multiple jokes about recent research, but the fact still stands — a lot more people know about those projects now than before the findings were worked into an SNL script.

Did you watch the November 12th episode of SNL? Do you remember which Weekend Update stories I’m talking about? No worries if you don’t — this post will refresh your memory, and take you beyond the one-liners.

With Emma Stone hosting and Coldplay performing, this past Saturday’s episode of SNL was already quite promising. However, when Seth Myers gave mention to not one, but two recent findings that I had come this close to posting on Try Nerdy…I was tickled.

Here’s a clip from Weekend Update that starts with the first nerdy reference (34:47) and ends with a second one (36:12):

The clip begins:

Researchers say that a new drug tested on monkeys has helped them lose weight with no dieting or exercise – it’s the easiest way to make the lean, sexy monkeys we’ve all been clamoring for.

Aside from being hilarious, this punchline makes a point — sometimes, research sounds ridiculous to the Average Joe. Whether it’s “fruit flies in France” or “sexy monkeys,” it’s not always immediately obvious how animal research relates to us as people. The common idea behind this type of research is that all living organisms — humans, monkeys, and, yes, fruit flies — are related on a big evolutionary tree, and that important biological mechanisms are probably conserved between us, or at least similar.

So about those monkeys. Monkeys are relatively quite close to humans on an evolutionary scale, so the discovery of a drug that makes obese monkeys lose weight effortlessly is kind of a big deal. Something that works in monkeys has a higher likelihood of working in humans, too. These monkeys, who became obese through overeating and under-activity, were given a drug that selectively destroyed the blood supply of fat tissues. Without a blood supply, the fat in these monkeys was broken down and reabsorbed.

Here’s fat in its normal state, thriving on a nutritious supply of blood:

Then this drug, called adipotide, kills the blood vessels supplying the fat, and the fat effectively melts away (the monkeys lost nearly 30% of their abdominal fat!):

If this drug gets approved for humans, it would be radically different from other weight loss drugs on the market, which typically try to suppress appetite or block absorption of dietary fats.

Near the end of Weekend Update, Seth surprised me again with another story that very nearly made it onto this site:

A new study suggests that people with high blood pressure suffer from emotional dampening and have trouble recognizing emotion in others – they’re called dads.

This got a laugh, but it basically summed up a study done at Clemson University in South Carolina. Researchers asked 106 participants to evaluate emotional expressions in faces and sentences, and individuals with higher resting blood pressures were significantly less accurate at the task. Imagine the irony: your job is super stressful, which drives your blood pressure up, which induces “emotional dampening,” which makes you interpret your boss’s constructive criticism as sarcastic prattle (which will probably lead to more stress down the line).

Oh, Mr. Steele, you're such a kidder.

The general idea at work here is that blood pressure can impact the central nervous system in complex ways; for example, hypertension is associated with decreased pain sensitivity. Perhaps a decrease in emotional sensitivity is part of the same phenomenon. Time (and more research) will tell, but until then, if someone misinterprets your words or fails to laugh at your joke, don’t get frustrated — maybe they’re just under a lot of stress…or eating a high-salt diet.

In any case, I’ll be paying closer attention to Weekend Update from now on, especially when I get blogger’s block.

Stay nerdy

 
Barnhart KF, Christianson DR, Hanley PW, Driessen WH, Bernacky BJ, Baze WB, Wen S, Tian M, Ma J, Kolonin MG, Saha PK, Do KA, Hulvat JF, Gelovani JG, Chan L, Arap W, & Pasqualini R (2011). A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Science translational medicine, 3 (108) PMID: 22072637

McCubbin JA, Merritt MM, Sollers JJ 3rd, Evans MK, Zonderman AB, Lane RD, & Thayer JF (2011). Cardiovascular-emotional dampening: the relationship between blood pressure and recognition of emotion. Psychosomatic medicine, 73 (9), 743-50 PMID: 22042880

You may not exactly like the things you learn about fat in today’s post, but fat seems to be society’s public enemy number one lately, and you know what they say — it’s always best to know your enemy.

Here’s a fat cell:

It’s relatively huge as far as cells go. With a diameter of about a tenth of a millimeter, it’s over 100 times the size of a skin cell, and just one fat cell is potentially visible by the naked eye. As you can see, most of a fat cell is a huge pool of fat, with all of the other parts of the cell squished off to the side. If you’re the average adult, you’ve got about 30 billion of these guys. All the more reason to know what they’re capable of, right?

1. Fat cells can pilfer your medications and vitamins. At the most basic level, when you take medicine or vitamins, your body uses what you need and the byproducts or whatever your body doesn’t use are excreted. However, many vitamins (like A, D, E, and K) and medications (including many antidepressants and anesthetics) are fat-soluble, as opposed to water-soluble, meaning that as they circulate your body they can slip out of your blood and into your fat. THC, the active compound in marijuana, is an example of a fat-soluble drug; if an obese person with large amounts of body fat gets high with a skinny person with low levels of body fat, it is likely that the obese person would test positive for a longer stretch of time, because the obese person has more fat cells to trap the THC and release its metabolites more slowly over time.

Sneaky fat cells…

2. Fat cells influence how hungry you are and whether or not you get diabetes and heart disease. As it turns out, fat cells don’t just take stuff out of your blood, they put stuff in it, too. In particular, fat cells make a whole bunch of hormones and inflammatory molecules. One of the most important molecules made by fat is leptin, which signals to the brain and decreases appetite. Mice without receptors for leptin become obese:

Fat tissue also releases inflammatory molecules called cytokines that can decrease the ability of the body to respond to insulin, which can set the stage for diabetes. Some of these inflammatory molecules are also thought to promote systemic inflammation, and research suggests that this can make atherosclerosis (artery blockage due to fat accumulation) all the more dangerous. That’s because inflammatory cells might be able to rupture atherosclerotic buildup, creating clots that induce heart attacks or strokes.

This is a lot of information to take in, and the many roles of fat as a signaling tissue make up a very active area of research right now, especially because fat can often turn on or off production of specific molecules in obese individuals.

3. Fat cells can feed cancer cells. If you weren’t hating fat by now, this might just tip the scales. Very recent research in Nature Medicine suggests that abdominal cancers, like ovarian cancer, are made worse by fat. Ovarian cancers tend to metastasize to fat-dense regions of the abdomen, and fat cells can directly transfer fat to cancer cells, which provides the cancer with energy and allows it to grow in size.The silver lining of these findings is that researchers may now have a new mechanism to target when designing drugs to fight cancers that flourish in fatty areas of the body.

4. Fat cells might be the cure to just about everything. Alright, last but not least, a major redeeming feature of fat: it’s got stem cells in it. In general, stem cells are cells that have the potential to differentiate into multiple other cell types. Scientists have theorized stem cells to be a potential therapy for just about every disease condition (e.g. using stem cell-derived neurons to replace the lost/damaged neurons in neurodegenerative diseases). Although fat stem cells can’t turn into as many cell types as embryonic stem cells can, they have many upsides: fat stem cells circumvent ethical concerns, are readily available thanks to all of the fat-removing surgeries done today, and pose far less risk of immune rejection when re-introducing cells taken from someone’s own fat. Fat stem cells have already been shown to essentially cure a mouse model of lupus.

So maybe you’re not necessarily any happier about your fat now, but I hope you have a new appreciation for it. While you lament your muffin top, you can consider the diverse biology of your muffin top. That might sound nerdy, but…well, that’s the whole point.

Ovchinnikova O, Robertson AK, Wågsäter D, Folco EJ, Hyry M, Myllyharju J, Eriksson P, Libby P, & Hansson GK (2009). T-cell activation leads to reduced collagen maturation in atherosclerotic plaques of Apoe(-/-) mice. The American journal of pathology, 174 (2), 693-700 PMID: 19131590

Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, Romero IL, Carey MS, Mills GB, Hotamisligil GS, Yamada SD, Peter ME, Gwin K, & Lengyel E (2011). Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nature medicine, 17 (11), 1498-503 PMID: 22037646

Choi EW, Shin IS, Park SY, Park JH, Kim JS, Yoon EJ, Kang SK, Ra JC, & Hong SH (2011). Reversal of serological, immunological and histological dysfunction in systemic lupus erythematosus mice by long-term serial adipose tissue-derived mesenchymal stem cell transplantation. Arthritis and rheumatism PMID: 21904997

Yeah, you should check this out:

The authors started off by looking at the genes expressed in muscle biopsies from muscles undergoing atrophy, and they made note of which genes had high or low expression. Then, they screened 1300+ compounds for any that could (basically) decrease the high genes and increase the low genes, the idea being that any compound that could reverse the gene expression in muscle atrophy might be a good treatment. And they were right.

Ursolic acid

The screen identified ursolic acid, a compound found in large quantities in apple peels, as the only potential inhibitor of muscle atrophy. So the researchers injected ursolic acid into mice with atrophic muscles, which stopped muscle loss and increased muscle weight by 7%. Seven percent might not sound like a lot, but it is, considering that, again, this is the first compound shown to stop muscle loss at all. A 7% increase in muscle weight in a 180 lb man with typical muscle mass would mean a gain of over 5 pounds of muscle.

Ursolic acid diet shrinks fat cells

Things got even more interesting when normal mice were put on a diet with 0.27% ursolic acid: muscles got bigger and significantly stronger, blood levels of fat and cholesterol decreased, and fat cells shrank considerably, thus reducing fat weight significantly (see for yourself in a figure from the article, left). This is all in addition to the lowered blood sugar in fasting mice who received ursolic acid injections. To make things even better, the authors were able to identify genes that were increased or decreased by treatment, and that were probably responsible for these effects.

In my opinion, these scientists stumbled across something even greater than what they hoped to find. Their data on ursolic acid suggests its usefulness in treating everything from muscle atrophy to obesity to metabolic syndrome to type 2 diabetes. Not even mentioned in this paper is the work that has previously shown the ability of ursolic acid to inhibit cancer cells and Alzheimer’s proteins.

Okay, I’m impressed. What doesn’t ursolic acid do? Seems like it could be a future wonder drug! I’m very interested to see what scientists will try with this compound next…

Have a nerdy weekend!

Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, & Adams CM (2011). mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. Cell metabolism, 13 (6), 627-38 PMID: 21641545

Shishodia S, Majumdar S, Banerjee S, & Aggarwal BB (2003). Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase 2, matrix metalloproteinase 9, and cyclin D1. Cancer research, 63 (15), 4375-83 PMID: 12907607

Pathak AK, Bhutani M, Nair AS, Ahn KS, Chakraborty A, Kadara H, Guha S, Sethi G, & Aggarwal BB (2007). Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells. Molecular cancer research : MCR, 5 (9), 943-55 PMID: 17855663

Wilkinson K, Boyd JD, Glicksman M, Moore KJ, & El Khoury J (2011). A high-content drug screen identifies ursolic acid as an inhibitor of amyloid-{beta} interactions with its receptor CD36. The Journal of biological chemistry PMID: 21835916