This research article is titled "Obesity in mice with adipocyte-specific deletion of clock
component Arntl".
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
its 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 in 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 this 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 we spend and whatever is not spent is stored.
There are many things that affect energy balance such as obesity and undernutrition 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 rhythm
or internal clock.
So what is a circadian rhythm?
Our bodies function on a 24 hour clock that is influenced by the day/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/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 cycle 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
Arntl ONLY in adipocytes.
They next fed the mice a high fat diet and looked at the mice's body weight compared
to normal mice with an intact circadian rhythm.
mice that had a disrupted adipocyte circadian rhythm were heavier and had 50% more fat than
normal mice: they became obese!
To explain the development of obesity, the scientists looked at a variety of factors:
- physical activity
- how many calories the mice ate
- how much energy the mice spent
- at what time of the 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!
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.
So the scientists fed normal mice the same number of calories either only at night or
only during the day and they saw a higher rate of obesity in mice fed during the day
than at night.
so shifting the timing of food intake alone was sufficient to cause obesity in mice!
Scientists think that this is because eating at an inappropriate time (at 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 toward weight gain and leading to obesity.
There is actually evidence for this in humans: night shift workers eat at night, have a dysregulated
circadian rhythm, and have an increased prevalence of obesity and 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 (because it's not in line with the central
internal clock) and causes weight gain.
So the scientists were curious to understand exactly how adipocyte circadian clocks could
control the timing of food intake that leads to obesity in these mice.
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 is high so the mice are not hungry.
at night, these levels drop so the mice get hungry and they eat.
The scientists realized that mice with a 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 will eat at night and gain less weight.
In fact, when the scientists fed mice that had a disrupted adipocyte circadian rhythm
a high fat diet supplemented with polyunsaturated fats, the mice did not become obese!
they ate at a normal time of day (at night), and the had normal energy expenditure, overall
they looked just like normal mice.
this means that the low levels of polyunsaturated fats in mice with a disrupted adipocyte circadian
rhythm is responsible for the development of obesity by increasing food intake during
the day and decreasing energy consumption.
(maybe say that depending on time)
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 a 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 is 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 this 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 fun
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 the 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 rhythm maybe by providing more polyunsaturated fats in
the diet.
But too much of anything is bad so this requires 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!