It has been known that excess energy is stored in fat cells, which signal these levels to the brain. Now, scientists have discovered that deleting the clock gene Arntl in fat cells leads to obesity in mice, and also causes a change in the timing of their normal eating schedule.
The finding, published in Nature Medicine, came from Georgios Paschos, PhD, a research associate in the lab of Garret FitzGerald, MD, FRS director of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania.
The research gives insight into the complicated causes that make people obese. The findings were unexpected for a couple of reasons.
Paschos explained: “The first is that a relatively modest shift in food consumption into what is normally the rest period for mice can favor energy storage. Our mice became obese without consuming more calories.”
If the experts copied the changed pattern of food consumption that was seen in mice with a broken clock, which is also referred to as Bmal1, in their fat cells, the normal mice could also become obese.
The night-eating condition that some people experience is relatively similar to the changes in behavior seen in the mice. This syndrome was linked to obesity by Albert Stunkard, also from the University of Pennsylvania, in 1955.
The other discovery has to do with the molecular clock. Clocks in peripheral tissues are generally believed to be guided by the action of the “master clock” in the SCN of the brain.
“While we have long known that peripheral clocks have some capacity for autonomy – the percussionist can bang the drum without instructions from the conductor – here we see that the orchestrated behavior of the percussionist can, itself, influence the conductor,” FitzGerald added.
Oscillating expression of genes that trigger and subdue hunger in the hypothalamus is what drives the intake of food each day. The scientists found that this hypothalamic rhythm pattern was interrupted when the clock was broken in fat cells in order to favor eating at the time of inappropriate intake, which is during the day for mice and during the night for humans.
When the daily norm is changed, the metabolism is changed as well. People who work at night, for instance, have a higher chance of obesity and metabolic syndrome, and individuals struggling with sleep problems have an increase chance of obesity. It is also easier to gain weight with less sleep for healthy males and females.
The body needs to combine several signals between the central nervous system and outlying tissues, including the heart and liver, in order to balance energy levels.
Fat cells are responsible for storing and releasing energy as well as communicating with the brain, through the hormone leptin, regarding the amount of energy that is stored. The body uses more energy and eats less when leptin is secreted through pathways in the hypothalamus.
The experts realized that when the clock was broken in fat cells, just a small number of genes had been changed, and this is what determined how unsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were allowed into the blood stream. These fatty acids are normally linked to fish oils. At the time of unsuitable eating, levels of these acids were low in plasma and in the hypothalamus.
“To our amazement, we were able to rescue the entire phenotype – inappropriate fatty acid oscillation and gene expression in the hypothalamus, feeding pattern and obesity – by supplementing EPA and DHA to the knock-out animals,” said Paschos.
Through the research, the role that the fat cell clock molecules play in regulating energy and the timing of food consumption was seen – by contact with the hypothalamus, which in the end, impacts energy that is stored as well as how much a person weighs.
These reports stress the crucial role that the molecular clock plays in metabolism, while also showing the main part fat cells play in the process of taking in food and using energy.
“Our findings show that short-term changes have an immediate effect on the rhythms of eating. Over time, these changes lead to an increase in body weight. The conductor is indeed influenced by the percussionist.”
Written by Sarah Glynn