 This research article is titled Obesity in Mice with adipocyte-specific deletion of clock component arntal. It was published by the Fitzgerald lab at the University of Pennsylvania in Nature Medicine in December 2012. To start talking about this article let's understand what energy balance is and how it's controlled. Energy balance is an equilibrium between the energy we take in and the energy we spend. We get energy in the food that we eat and we spend energy by moving around, breathing, etc. In order to maintain a certain body weight our bodies need to be an energy balance meaning the amount of energy we take in is equal to the amount of energy we spend. If we take in more energy than we spend then the energy is stored in fat and we gain weight. So we can write this equation. The energy we take in in the form of food is equal to the energy that we spend and whatever is not spent is stored. There are many things that affect energy balance such as obesity and under nutrition but also thyroid disease and diabetes among many others. So it's important to understand how energy balance is maintained and what happens when energy balance becomes imbalanced. This article tries to understand how energy balance is controlled by our circadian rhythms or internal clock. What is a circadian rhythm you may ask? Well our bodies function on a 24 hour clock that is influenced by the day and night cycle that controls sleep, alertness, digestive activity, etc. One obvious example of the importance of this circadian rhythm is jet lag. When our body's circadian rhythm is not synced to the day and night cycle so we are sleepy and hungry at the wrong time of the day until our body tries to adjust to a new day night cycle. So our circadian rhythm can influence our eating behaviors and therefore our energy balance. This circadian rhythm I'm talking about is the central circadian clock that responds to the day light cycles to control behavior. But there are also circadian rhythms specific for different tissues that are synced with the central circadian clock and that control the behavior of that specific tissue. The scientists of this article are interested in studying the circadian rhythm in the cells of the fat tissue which we call adipocytes. Because energy is stored as fat, fat tissue plays a crucial role in energy balance. So the scientists wondered what role this fat or adipocyte specific circadian rhythm played in energy balance. To do this, the scientists used the mouse. They disrupted only the adipocyte circadian rhythm by genetically removing a protein called arntal only in adipocytes. They next fed mice a high fat diet and looked at the mice's body weight compared to normal mice with an intact circadian rhythm. So mice that had it disrupted adipocyte circadian rhythm were heavier and had 50% more fat than normal mice. In other words, they became obese. To explain the development of obesity, the scientists looked at a variety of factors. First, they looked at physical activity. Then they looked at how many calories the mice ate, how much energy the mice spent, and at what time of day the mice ate. The scientists found no differences in physical activity between the two groups and no differences in the calories consumed. So the mice exercised just as much and ate just as much food yet they were heavier. So what could explain these differences? Well, it turns out that mice with a disrupted adipocyte circadian rhythm spent less energy and ate more during the day and less at night compared to normal mice who eat more at night and less during the day. So it seemed that eating the same number of calories during the day instead of at night could cause obesity in these mice. Scientists think that this is because eating at an inappropriate time or a time that does not line up with your central clock will cause your body to store instead of spend the energy shifting the energy balance towards weight gain and leading to obesity. There's actually evidence for this in humans. For example night shift workers eat at night and they have a dysregulated circadian rhythm and an increased prevalence of obesity in metabolic diseases. So it seems like these mice with dysregulated adipocyte circadian rhythms eat at a different time of day. This reduces the amount of energy they spend and causes weight gain. So the scientists were curious to understand how adipocyte circadian clocks could control the timing of food intake that leads to obesity in these mice. Well the timing of food intake is influenced by levels of polyunsaturated fats in the blood. These are good fats that can benefit your health when eaten in moderation. So in mice during the day levels of these fats are high so the mice are not hungry but at night these levels drop so the mice get hungry and they eat. The scientists realized that mice with the disrupted adipocyte circadian rhythm had lower blood levels of polyunsaturated fats during the day. This is because these mice were releasing less polyunsaturated fats into the blood despite consuming the same amounts of fats as normal mice. So the scientists wondered if maybe these low polyunsaturated fat levels were responsible for the increased food intake during the day. If this is true then increasing levels of polyunsaturated fats in these mice should prevent weight gain because the mice will not be hungry during the day so they will not eat during the day but instead they will eat at night and gain less weight. In fact when the scientists fed mice that had disrupted adipocyte circadian rhythm a high fat diet supplemented with polyunsaturated fats the mice did not become obese and they ate at a normal time at night and they had normal energy expenditure. Overall they looked just like normal mice. So what did this study show? Using a mouse to genetically disrupt the circadian rhythm specifically in the adipocytes or the fat tissue the scientists showed that these mice became obese not because they ate more calories overall but because they ate more calories during the day instead of at night. This is because it disrupted circadian rhythm in the adipocytes causes lower levels of polyunsaturated fats in the blood during the day. This makes the mice more hungry during the day when feeding is normally low. For mice eating more during the day instead of at night causes a shift in the energy balance and energy stored instead of spent leading to obesity. So this study shows that circadian rhythms in your fat tissue control timing of food intake and energy balance that can cause obesity when the circadian rhythm is dysregulated. So what does this mean for you? The rate of obesity has increased extraordinarily over the past 100 years so it might be a friend to consider the relevance of this study in the context of evolution. Certainly the increase in obesity is due to more calories in our diet and less exercise but what if timing of food intake also played an important role? In any major city you can get food delivered to your door 24 hours a day. You can imagine that this was a lot more difficult 100 years ago. So what if availability and consumption of food at night when our bodies are not supposed to be eating but sleeping is contributing to the higher rates of obesity nowadays. As we try to understand how weight is controlled this study shows that it's also important to consider circadian rhythms in the fat tissue that can control when we get hungry. Although follow-up studies in humans need to be done this article provides a mechanism we can try to target to control weight gain in individuals with sleep disorders or just generally dysregulated circadian rhythms maybe by providing more polyunsaturated fats in the diet. But too much of anything is a bad thing so this would certainly require a delicate balance. Scientists are always trying to understand how pathways in this case two different internal clocks can work together to explain the complexity that lies behind every aspect of physiology from blood levels of polyunsaturated fats to the psychology of chocolate cravings.