Shiver Me Thinner?

In making the move from the sunny desert of the southwest to the chilly northeast I've often wondered what this harsh climate is doing to my body. Of course my mind automatically goes to all of the bad things caused by extreme cold - hypothermia, slipping on ice, liver failure from all of the whiskey needed to keep warm - but turns out there may be some metabolic advantages to being in a cold environment due to a potential increase in a type of fat tissue called brown adipose. While brown adipose has become a growing area of research in recent years, it was originally discovered decades ago. The reason for the newly found interest is because until recently it was thought that only newborn babies and non-human mammals had brown adipose. The belief was that as newborn babies grew into adolescents they lost the brown adipose and were left with the normal white adipose tissue. So why does discovery of this special type of fat in human adults matter? Because it may increase the use of energy from the food that we eat for heat production in a process called non-shivering thermogenesis, which gives the body a mechanism to provide heat when living in a cold environment. Because this energy is being "burnt off" as heat, it won't be stored in your growing beer belly. So maybe you can't shiver yourself thinner, but maybe you can non-shiver yourself thinner.

The name "brown adipose tissue" comes from the look of this tissue under a microscope. It's brown, and it's adipose tissue. Sometimes science can be straight-forward. The brown color is from extra mitochondria, which are the organelles within the cell that make energy (in the form of ATP) for your body. In order to do this, the mitochondria keep an electrical gradient across its inner membrane by separating the negatively charged electrons from the positively charged protons (in the form of hydrogen atoms). The electrons then are transported through a series of proteins collectively called the electron transport chain (again, straight-forward), until the end of the chain. At this point the positive hydrogen atoms are allowed to flow back through the membrane, releasing energy that is refashioned into ATP molecules by the enzyme ATP synthase (See the picture below for the cartoon rendition of the ETC). These molecules are then passed on to every cell in the body, keeping us alive. So you can imagine that if this simple flow of hydrogen atoms down the energy gradient holds enough energy to keep each cell going, it also must be able to release that energy as heat. This is where we get back into brown adipose tissue and non-shivering thermogenesis. There is a protein called Uncoupling Protein (UCP) that is highly expressed in brown adipose. UCP will basically give the hydrogen atoms another channel to travel through the mitochondrial membrane down the energy gradient. This time instead of using that energy to make ATP it is released as heat, thereby raising the body temperature. This switch-over from ATP production to heat production causes the body to want to make more ATP, so the energy stores in your body that are the starting substrates of the reaction start to get used up.

Remember the ETC?

Those of you that are pharmacological-minded may ask why we don't just make a weight-loss drug that uncouples the electron transport chain? Well...because it's a poison. Back in the 1930's people started taking an ETC uncoupling chemical called dinitrophenol, DNP for short, to lose weight. It worked great! But, it also resulted in your mitochondria not being able to make any ATP for your cells to survive. No ATP = no energy = no you! Unfortunately it looks like there is still an illegal market for DNP and people are still taking it. This is pretty scary stuff, I don't think you want to mess with cellular respiration. Plus it seems the body does this for you to a degree if you have brown adipose tissue, which you probably do. The amount of brown adipose that you have seems to be correlated with age (the younger you are, the more you have), sex (females have more), fasting blood glucose (a lower fasting glucose is associated with more brown adipose), and BMI (the leaner you are the more non-shivering you may potentially do). Interestingly, the activity of the brown adipose seems to correlate with the mean outdoor temperature of where you live, so that the warmer the climate, the more glucose is taken up by the brown adipose and potentially used for heat production (See graphs below). This study just so happened to take place in Boston, so these subjects also get to experience the New England chill alongside me.

Yes, you read that right, those with a lower BMI actually seem to have more brown adipose. Why? Well, maybe they need more heat because they have less fat to act as insulation, or maybe it's the extra brown adipose that is letting them stay thinner in our obesogenic environment, no one really knows yet. Also something interesting to note, those with a lower BMI or % body fat also had more active brown adipose tissue, meaning the tissue is taking up more glucose out of the blood (see graph below). 

Okay, so I guess I take back my previous statements, you probably can't shiver yourself thinner, or non-shiver yourself thinner, but maybe when you are thin you can non-shiver yourself warmer? 

van Marken Lichtenbelt, WD. et. al. Cold Activated Brown Adipose Tissue in Healthy Men. New England Journal of Medicine (2009)

Cypess, AM. et al. Identification and Importance of Brown Adipose Tissue in Adult Humans. New England Journal of Medicine (2009)

Bartelt, A., Merkel, M. & Heeren, J. A new, powerful player in lipoprotein metabolism: brown adipose tissue. Journal of Molecular Medicine (2012)

Raspberry Ketones and Your Love Handles

In addition to spending my days chained to the lab bench, I also spend my time moonlighting as a teaching assistant for nutrition classes in the Boston area. In one such class the students were given the assignment to present a nutrient or food that is associated with preventative properties of certain diseases. One student group decided to focus on what is seemingly the next diet craze: raspberry ketones (RK). I thought this would would make a great Scienticklish post because it is a timely topic (having recently been aired on Dr. Oz) and the immediate anger I felt after Googling RK and weight loss and finding so much bad information riddled with lies! Thus, a post to get the facts out there. Science!

First, some background. Raspberry ketones are small molecules found naturally in red raspberries which give them their smell and flavor (see above for the molecular structure). RKs have been used by the food industry for years to put the flavor or raspberries into various treats. They are also used in various perfumes, soaps and lotions, so the synthesis and purification of RKs are nothing new. In the past decade some scientists started taking note of the molecular similarities between RK and capsaicin - the molecule that is responsible for chilies' spiciness that have been shown to increase metabolic rate. Intrigued by this resemblance, researchers in Japan began to study the effects of feeding RK to mice that were eating a diet high in fat. They published a study in 2005 that showed feeding RK to these mice increased lipolysis, or breakdown of fat and decreased the absorption of dietary fat. Overall, the mice fed larger doses of RK were lighter than the mice fed the high fat diet alone (See figure below). A high dosage seemed to be key: the mice that were fed a diet containing 2% RK by weight had a significant decrease in body weight, but the group of mice eating a diet that was either 0.5% or 1% RK by weight did not have any difference in body weight relative to mice fed a high fat diet alone. It's probably safe to bet that the amount of RK needed to see this effect is not available by simply eating raspberries, which brings us to the next published paper I'll discuss: a patent!

ND: Normal Diet;  HFD: High Fat Diet;  RK: Raspberry Ketone

Also in 2005, a different research group (associated with DSM, a leading producer of purified nutrients that are used in supplements and food products globally) published a US patent for a neutraceutical blend of the polyphenol found in green tea called EGCG and an RK precursor. This patented product demonstrated the ability to  prevent weight gain and obesity associated conditions (like type II diabetes), again, in rodents. Showing similar results, their now patented supplement prevented weight gain in both mice and rats fed a high fat diet or a high fat, high sugar diet.

So, should you be taking RK to get ready for the beach this summer? Well, so far it hasn't been shown to have any adverse effects (other than decreasing the size of your summer beer fund), but because published research in humans is so limited (i.e. non-existent), no one really knows if it is safe. More and more nutrition research is coming out to show that supplementation of large doses of a single nutrient are actually harmful for humans, so you should take caution before popping pills of any kind. Plus keep in mind that RK supplementation has only been shown to prevent rapid weight gain in mice that were eating a very high fat diet, you can't expect that it's going to behave the same in humans that are trying to lose weight. The nutrition community goes through these magical weight loss nutrients so quickly without much to show for it. Remember when I said the idea of using raspberry ketones for weight loss stemmed from using capsaicin for weight loss? Well, do you know anyone that has lost a lot of weight by taking capsaicin pills? Right. I hate to be the negative Nancy here, but the best way to lose weight is really to make some major lifestyle changes that include eating foods that will keep you fuller longer (high fiber, high protein), and constantly reminding yourself to keep moving. Yes, it's going to be hard and you're probably rolling your eyes at the nutrition community for sounding like a broken record, but it is what it is. In the end, you'll be better off trying to increase your intake of raspberries (along with other fruits and vegetables) than spending that cash on pills.

Yum!

Morimoto, C. et al. Anti-obese action of raspberry ketone. Life Sciences (2005)

Raederstorff, D. et al. Nutraceutical compositions comprising epigallocatechin gallate and raspberry ketone. US Patent Office (2005)

The Evolution of Cuteness

It’s one of my favorite stories in science: why we are programmed to think our babies are so damn cute. Besides giving parents bragging rights and feelings of pride and adoration, having our brains programmed to think our offspring are cute comes with evolutionary advantages. To better understand what those advantages are we will need to take a step back into the times when our ancestors were still spending most of their days swinging from branch to branch rather than running around on two legs. We needn’t be too imaginative, just think of how an ape moves around. Most of its time (when not adorably hanging around) is spent on 4 limbs. This means the joint between the hip and the upper femur doesn’t need to be able to bear a lot of weight. Because of this, the shape of the pelvis of an ape was, and still is, very different from the pelvic bone of a human. 

About 6 million years ago, the early human ancestors came down from the trees and began to discover all that the grasslands had to offer. Why? I think they were probably just sick of eating tree fruits all day and craved adventure! Due to this drastic lifestyle change, the skeletal structure of early hominids began to change as well. The hip began to adjust so that all of the body weight could be put on only two limbs for a significant amount of time. As the hip evolved to be more compact, so too did the birth canal which narrowed to give more strength to the hips for bipedalism. A smaller birth canal would be okay for your monkey-brained neighbor, but not for the superior intellect of yourself. As we went from apes to hominids the brain and the head size began to develop as well. This poses an obvious problem in human evolution: how on earth are we supposed to give birth to babies with increasing brain and head sizes while at the same time develop a narrowing birth canal? 

Schematic drawing of the birth canal sizes and fetal skull sizes in apes and humans. Looks like humans have it pretty bad!

An interesting conundrum, and one we have thankfully overcome! If you have spent any time around a newborn you know how completely helpless they are. Newborns need a more capable being to help them eat, burp, even hold their head up. Given that the size of human brains are substantially larger than other mammals that are completely capable upon birth, does this not strike you as odd? Additionally, consider the length of gestation for us humans. Nine months is a relatively long time, especially when the end product isn’t quite ready for life on its own. While fetuses are in the womb their brain and head size will develop to be as big as possible while still small enough to pass through the narrow birth canal. Then, after birth, the baby’s brain will continue to grow as the baby becomes more able to perform tasks like eating and holding a spoon. The soft connective tissue, or fontanels, connecting regions of the skull at birth will eventually fuse when the skull has reached its proper size. For quite some time after birth however, infants are dependent on others to help them survive. Without this help, infant survival would be impossible.

Enter the cuteness factor! Lucky for all of us parents have a natural affinity for their offspring when they are brought into this world because they’re perceived as cute! The baby fat, the forward facing, large round eyes and button nose all contribute to why we think infants (and some baby animals for that manner) are cute; and part of the reason why parents feel a compelling need to stick around and care for them. This has been given the technical, German term of Kindchenschema, roughly meaning childlike cuteness in some scientific literature. Interestingly enough, the ability to correctly select the “cuter” baby when presented with a cute and a less-cute picture of a chubby-cheeked test subject is stronger in women (see the photos below for an example). Perhaps Kindchenschema is another way, in addition to the oxytocin release women experience while breastfeeding their newborn, that the maternal instinct shapes new moms. 

Because cuteness makes something click in the parents’ brain causing them to want to care for the infant, the baby is given time to develop its brain and fuse its fontanels. Of course there are other theories of why newborns are seen as cute, one of which is simple natural selection. As the the theory goes, the children that were seen as the cutest got more food, love and attention from their parents, thereby growing up to be strapping, fertile adults that could pass along their cute-genes to their own plethora of offspring. This is a noteworthy theory, but I like to think that the evolution of cuteness derives from the infant’s need for love and attention right at birth. So in the end, when humans started to walk around and gather their food, babies started finding out a way to make us unconditionally love them. Those maniacal babies!  

Insert devious laughter here. 

1. Rosenberg, K. & Trevathan, W. Birth, obstetrics and human evolution. BJOG (2002)
2. Lobmaiera, JS. et al. Female and male responses to cuteness, age and emotion in infant faces. Evolution and Human Behaviour (2010)