Nailing down a topic

This weeks has been a relaxing, occupied week. Compared with school, it's downright slack, but at least I have something to do during the day that isn't just time-wasting. I've alluded in the past to what I'm doing this summer, and now I know. I have to give a 10 minute talk (with flannelboard) about what I'm doing, so I'll give the loyal readers a sneak peak. Medical posts were not very highly ranked on the ol' survey-o-meter, so I'll try to keep this non-technical.

The liver, or as the French would say "le foi" (not to be confused with "la foi" - faith, a common missionary blunder) is the center of our focus. The liver metabolizes the fats and carbohydrates we eat. Excess of either are stored as triglyceride, which can simply be thought of as fat. What we're looking at mice who live on a diet rich in trans fat and high fructose corn syrup. Trans fats are not found in nature in very high quantities. They are made in the gut of ruminants, but not in great amounts. Trans fats are a by-product of the hydrogenation of natural oils, often soybean oil. Natural fats have reactive carbon bonds in them which can lead to rancidification, unless the bonds are modified. This modification involves heating and bubbling hydrogen into the oil to remove some of the double bonds. In the process, the orientation of the bonds is changed from a curved to a straight orientation. Saturated fats are fats from whom all of the double bonds have been removed, rendering the final product stiff like lard. Unsaturated fats have a few remaining double bonds, and are consequently more fluid and malleable.

Why should this organic chemistry affect you? Trans fat intake is associated with significantly higher risks of cardiovascular disease, as shown in several large epidemiological studies. It also has some disturbing effects on the liver, which is what we're studying. Our mice live a small, mousey, American life. They can eat all they want (known as feeding ad libitum), their diet is rich in trans fats, and their water is filled with high fructose corn syrup, so that they drink the equivalent of 8 cans of soda a day. We also remove the portions of their cage that they can climb on, rendering them much more sedentary.

When you examine the liver of the mouse (post mortem naturally), it shows changes known as steatosis, which means simply that lipids are accumulating in the liver. This occurs in humans too, in the context of obesity, alcoholism, diabetes, and also in cases of poisoning by certain toxins (CCl4 for the really curious). Steatosis is largely reversible, if the instigating stimulus is removed, i.e. diet modification or cessation of alcohol. If prolonged however, the accumulating fat kills the liver cells and causes inflammation, or steatohepatitis (fatty hepatitis). The inflammatory process can lead to fibrosis (scarring) which in the liver is known as cirrhosis. Most people associate liver cirrhosis with alcoholism, but it can occur just as easily in the context of excess lipid accumulation. In fact, under the microscope, cirrhosis looks the same, regardless of what caused it. Once the liver is cirrhosed, it no longer functions and needs to be replaced, either by transplant or resurrection.

When you look at the microscopic images of these fatty livers, the cells are filled with little droplets of lipid. Normally the body can mobilize stored lipids for energy, as in the case of prolonged fasting. Trans fats change that somehow, and we're hoping to clarify how. What I'm going to be determining is where in the cell the trans fats wind up. Are they stored in membranes? in the lipid droplet? This can be determined by analyzing the various classes of lipids and discerning which ones are enriched for trans fats (which, you recall, aren't there naturally). Once we know where they are, we can begin to postulate mechanisms for how they change lipid trafficking. Hopefully you could follow along with me, and if you're curious, I can give you the more detailed version via email.