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

Though this blog has already featured insects more than I would have imagined (i.e. at all), this post is about something I really feel the need to share. Because, every so often, I come across something for which the research is so overwhelmingly positive, I’m shocked that it’s not more well-known.

If you want to know what bees are up to now that could significantly impact human health, click on.

In short, bees are collecting this stuff called propolis. They collect it from plants and it’s sort of like sap, but apparently way more awesome. Bees use it to patch up the smaller holes in their hives, but researchers are using it on…everything.

1. Propolis and diabetes. In China, researchers gave propolis capsules to rats with type 2 diabetes. At the end of the experiment, rats who received propolis had significantly less sugar and fat in their blood, and more insulin, compared to diabetic mice who didn’t get propolis. Not bad for bee spackle. Given that almost 10% of the U.S. has diabetes, we need all the help we can get against this condition.

2. Propolis and ulcers. Stomach ulcers are no fun; they’re painful and can cause a lot of vomiting. Although 60% of stomach ulcers are caused by bacteria in the stomach, some cases occur after a person receives radiation, as with cancer treatment. So some compelling work in Egypt found that if mice were given propolis orally one hour before receiving radiation, they were largely protected against the formation of stomach ulcers. In fact, propolis-treated mice developed a whopping 75% fewer ulcers than untreated mice.

3. Propolis and burns. Anyone who has had a second-degree burn probably wouldn’t wish it on his worst enemy. Interestingly, researchers are still exploring what the best dressing is for these burns. A few weeks ago, a team in Brazil tried propolis. You’ve probably caught onto this pattern, but applying 5% propolis to second-degree burns on rats decreased inflammation and increased the rate of tissue repair. Look at this graph:

Pessolato et al. "Propolis and amnion reepithelialise second-degree burns in rats." Burns. July 6, 2011. Figure 6.

See those black bars that are way taller than the other bars? That’s showing the fact that burns treated with propolis produced a lot more collagen than untreated (gray bars) or tissue-grafted (white bars) burns after 1, 2, and 3 weeks into the experiment. Impressive stuff.

4. Propolis and atherosclerosis. I don’t think I need to give much preamble about atherosclerosis, but basically it’s when arteries become blocked because of fatty deposits, and it’s a serious risk factor for heart attacks. Lo and behold, when a different group from Brazil gave propolis to atherosclerotic mice, the condition of the animals improved. These mice were genetically predisposed to have high cholesterol and they were fed a high cholesterol diet to induce atherosclerosis. After 4 weeks of being given extracts from various types of propolis, the mice were sacrificed and mice who received propolis treatment had better ratios of good to bad cholesterol, and had smaller areas of atherosclerotic build-up.

Finally, if you still need more convincing…

5. Propolis and cancer. Glioblastoma is the most common and most detrimental type of brain tumor in humans. People with glioblastomas tend to only survive 1 or 2 years with treatment (3 months without). That’s why it’s pretty exciting that researchers in Brazil (Brazil is really on top of propolis) found that propolis slowed the growth of glioblastoma cells in their lab. Propolis was effective alone, and even more so in combination with a standard brain tumor drug.

What can’t propolis do? Glioblastoma isn’t the only form of cancer against which propolis has proven effective. These five scenarios I’ve described aren’t the only conditions in which propolis has been a successful treatment. I encourage you to do your research if you’re interested:

And/or consider picking up a bottle of the stuff:

If the research didn’t back it up, I wouldn’t advocate for it.

Li Y, Chen M, Xuan H, & Hu F (2012). Effects of encapsulated propolis on blood glycemic control, lipid metabolism, and insulin resistance in type 2 diabetes mellitus rats. Evidence-based complementary and alternative medicine : eCAM, 2012 PMID: 21716678

El-Ghazaly MA, Rashed RR, & Khayyal MT (2011). Anti-ulcerogenic effect of aqueous propolis extract and the influence of radiation exposure. International journal of radiation biology PMID: 21745002

Pessolato AG, Martins DD, Ambrósio CE, Mançanares CA, & de Carvalho AF (2011). Propolis and amnion reepithelialise second-degree burns in rats. Burns : journal of the International Society for Burn Injuries PMID: 21741176

Daleprane JB, da Silva Freitas V, Pacheco A, Rudnicki M, Faine LA, Dörr FA, Ikegaki M, Salazar LA, Ong TP, & Abdalla DS (2011). Anti-atherogenic and anti-angiogenic activities of polyphenols from propolis. The Journal of nutritional biochemistry PMID: 21764281

Borges KS, Brassesco MS, Scrideli CA, Soares AE, & Tone LG (2011). Antiproliferative effects of Tubi-bee propolis in glioblastoma cell lines. Genetics and molecular biology, 34 (2), 310-4 PMID: 21734835

This research suggests that a new way to prevent precancerous cells from developing could be to increase the amount of available DNA building blocks so that the DNA could be synthesized properly and with fewer additional mutations.

Title: Nucleotide deficiency promotes genomic instability in early stages of cancer development

Authors: Assaf C. Bester, Maayan Roniger, Yifat S. Oren, Michael M. Im, Dan Sarni, Malka Chaoat, Aaron Bensimon, Gideon Zamir, Donna S. Shewach and Batsheva Kerem

Date of publication: April 28, 2011

Direct link: http://www.cell.com/abstract/S0092-8674(11)00378-3

PMID: 21529715

Abstract: Early on in a cancer, cells are under a lot of stress to make enough DNA to supply all of the new rapidly growing and dividing cells. These authors noticed that when genes responsible for regulating cell growth were activated abnormally by oncogenes (genes that can turn normal cells into cancer cells), there was a significant decrease in the amount of DNA building blocks, also known as nucleotides. The lack of sufficient nucleotides led to increased mutations in the DNA, so it was a great find when the authors saw that providing the cells with a external source of nucleotides decreased the extent of DNA damage and diminished several cancer-like characteristics of the cells.

Methods: Skin biopsies were taken from healthy adults and skin cells called keratinocytes were grown from these samples. Some of the keratinocytes were immortalized by infection with a human papilloma virus (HPV), an infection that causes cells to become cancerous. The authors studied the effects of increasing the nucleotide pool of these cells internally, by activating genes responsible for nucleotide synthesis, and externally, by extracting nucleotides from healthy cells and providing them to immortalized cells. DNA synthesis and damage were analyzed, as well as the ability of the cells to grow on a material that cancerous cells, but not healthy cells, can survive on.

Results: After extensive DNA analysis to confirm that immortalized keratinocytes have difficulty synthesizing DNA and an increase in mutations, the authors show that this is due to a 2-to-5-fold decreased nucleotide in these pools — a level insufficient to faithfully support extensive cell growth rates. To prove that the low level of nucleotides was responsible for the problems with the DNA, the researchers extracted nucleotides from healthy keratinocytes and used them to treat the immortalized keratinocytes. This significantly increased the rate of DNA synthesis and decreased the amount of DNA damage. Additionally, immortalized cells treated with nucleotides failed to grow on a soft, jelly-like substance called agar, which is important because untreated immortalized cells and other cancer cells are able to grow on this surface — healthy cells, and immortalized cells treated with nucleotides, cannot. Similar effects were seen when the authors turned on the genes responsible for synthesizing nucleotides in these cells.

Bottom line: The most important time to intervene in cancer is early in its development, to stop rapid growth before it is out of control. Thanks to this research, it seems like one potential way to do this, perhaps regardless of the type of cancer, is to find a way to get more nucleotides to the cells so that fewer DNA molecules are damaged. The authors discuss the potential benefits of folate, which is an essential vitamin for metabolizing many cellular components, including nucleotides. Folate is required in the diet for normal DNA replication, and folate deficiency is correlated with the incidence of several types of cancer. Perhaps folate will one day be explored as a supplement to prevent precancerous growths from becoming full-blown tumors.

 
Bester AC, Roniger M, Oren YS, Im MM, Sarni D, Chaoat M, Bensimon A, Zamir G, Shewach DS, & Kerem B (2011). Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell, 145 (3), 435-46 PMID: 21529715