On Friday we posted a summary on the website of one of our latest publications. The paper was on perilipins – a type of protein that surrounds lipid droplets, and is important in the regulation of fat storage – and looked at how their expression is influenced by diet, exercise and energy balance. We found that endurance training and fat consumption affected perilipin expression, while strength training and insulin sensitivity did not.
Why should I care? you ask. What are perilipins to me? And that’s the challenge.
Here at CERG, the scope of our research in cardiovascular disease and exercise ranges from public health and fitness to underlying molecular mechanisms, with everything in between. We use a variety of grand epidemiological studies, comparative models and clinical studies.
From an academic perspective this is really important. Not only do we want to create successful treatment options for cardiovascular disease by means of exercise – we also want to know how they work. Conducting both top-down and bottom-up research is essential in order to achieve this. But when you want to explain your work to the public, the bare facts can seem dull if you don’t explain the context sufficiently.
Research that makes you go wow!
To be fair, a lot of our research has that immediate appeal, with an exciting conclusion at first glance. For example, aerobic interval training is more effective in increasing the peak oxygen uptake in myocardial infarction patients than usual care. That’s cool because peak oxygen uptake has been shown to be an accurate predictor of future health, so changing usual care could improve the prognosis for cardiovascular patients. Or; that even low levels of physical activity reduce mortality in people with metabolic syndrome. Lesson: even if you’re unable to exercise every day, every little bit counts! And there are plenty of other good examples…
Not-so-sexy, but still really cool research
But if the conclusion is that there’s a clear correlation between perilipins 2-5 and muscle fiber type 1; and aerobic interval training increased the expression of perilipin 2 and 3 by 101% and 105% respectively? It just doesn’t have that same ring to the uninitiated… So here’s a little more context, which hopefully will lead you to recognize that perilipins are cool, and you should care that we found a correlation between exercise (endurance only) and perilipin expression.
The body stores excess energy as triglycerides. Since these are hydrophobic, they aggregate as lipid droplets in the hydrophilic cytosol inside of cells. Perilipins (also known as PAT-proteins or PLINs) are a family of proteins coating these lipid droplets, and they have an interesting, but not fully understood role in regulating fat metabolism. As summarized in a 2007 review, under normal conditions, perilipin prevents cytosolic lipases from reaching lipid droplets, thus preventing them from being broken down to be used in metabolism. However, when there is an energy deficit, perilipin is altered through phosphorylation, and facilitates maximal lipolysis which generate lots of energy by metabolizing the triglycerides.
Small changes have big consequences
Both animal models and genetic studies have shown that perilipins matter, since small changes in them can have drastic consequences. For instance, a 2001 study showed that mice genetically engineered to lack perilipin 1 ate as much as their normal peers, but had 30% less adipose tissue. They found that the basal fat metabolism was elevated, yet interestingly these mice were unable to reach as high a level of fat metabolism when stimulated (as during energy deficiency). This indicates that not only is perilipin 1 necessary to protect the lipid droplets when extra energy isn’t needed, but it is also required for maximal lipolytic activity. The mice were protected from diet-induced obesity when fed a high-fat diet, but had an increased tendency to develop glucose intolerance and insulin resistance, meaning they were predisposed to type 2 diabetes.
Another fascinating study looked at the change of just two nucleotides in the gene encoding perilipin in humans, and found a connection to obesity and response to exercise. It had earlier been shown that individuals with the abnormal gene had an increased risk of obesity. Jenkins and colleagues then showed that those with the abnormal gene retained more fat after a 6-month endurance training program, and this blunted their maximal oxygen uptake (VO2max) adaptation to training. They concluded that perilipin variation could explain some of the differences between people with respect to training response and cardiovascular disease risk.
Are you convinced yet? There are lots of other interesting papers out there on perilipins, but this gives you an idea of the potential involved. Perilipin is a cool molecule, and understanding it better is very exciting! And now that you have a little more context, you can consider giving the paper summary another shot if you skimmed right past it in the first place.
Written by Hanna Sofie Ellingsen at CERG.