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What's the point of using fruit flies as models for human heart disease?
Fruit fly nonsense
I really despair at some of the utter rubbish that comes out of prestigious universities sometimes. Below is a story that was published last month. It's reporting a study of fruit flies (which don't naturally eat fat) and extrapolating results to humans who do naturally eat fats. And dietary choices are only one difference between fruit flies and humans; there are many more. Some are obvious, others less so. But the differences are so great that about the only thing we have in common is that we are both carbon based.
First is the story as reported on Newswise, then some anatomical 'news' about the way fruit flies' blood circulation systems work (which is fascinating – did you know that fruit flies have 9 hearts?). Lastly a comment – if it is needed!
Learning About High Cholesterol, Obesity From Fruit Flies
Released: 12/2/2009 12:20 PM EST
Source: University of Utah Health Sciences
Newswise — How do fruit flies get high cholesterol and become obese? The same way as people do – by eating a diet that's too rich in fats.
More importantly, according to two new studies led by a University of Utah human geneticist, fruit flies use the same molecular mechanisms as humans to help maintain proper balances of cholesterol and a key form of stored fat that contributes to obesity. The findings mean that as researchers try to learn more about the genetic and biological processes through which people regulate cholesterol and fat metabolism, the humble fruit fly, also called Drosophila, can teach humans much about themselves.
"Not a lot is known about these regulatory mechanisms in people," says Carl S. Thummel, Ph.D., professor of human genetics at the U of U School of Medicine and senior author on the two studies. "But we can learn a lot by studying metabolic control in fruit flies and apply what we learn to humans."
High cholesterol and obesity, which affects an estimated 25 percent to 30 percent of the U.S. population, are linked to heart disease, diabetes, and other diseases that take huge tolls on health and add billions of dollars to the nation's medical bills. Understanding the processes that regulate cholesterol and fat in humans could be critical for addressing those health risks in people, Thummel believes.
The two studies identify a nuclear receptor, DHR96, which plays a critical role in regulating the balance or homeostasis of cholesterol and another fat molecule called triacylglycerol (TAG). Nuclear receptors are proteins that sense the presence of chemical compounds within cells. DHR96 corresponds closely to a nuclear receptor in humans, called LXR, that is known to regulate cholesterol levels.
In a study published Dec. 2 in Genes and Development, Thummel and colleagues at the U of U and two Canadian universities show that DHR96 helps regulate cholesterol in fruit flies by binding with this compound. When this binding occurs, it allows DNA to be read, which switches genes on and off that help maintain proper levels of cholesterol, according to Thummel, who also holds an H.A. and Edna Benning Presidential Endowed Chair in Human Genetics.
The researchers used a technique developed by University of Utah biologist Kent Golic, Ph.D., in which they silenced or disabled the DHR96 protein so it couldn't function in fruit flies. They then grew flies in which DHR96 was silenced. Depending on what the fruit flies were fed, lean or fat diets, they had either too little or too much cholesterol. Flies fed too little cholesterol died, while those with too much developed hypercholesterolemia or chronically excessive cholesterol levels. At the same time, flies in which DHR96 functioned normally maintained a proper level of cholesterol.
"When they lacked the DHR96 receptor, the flies were unable to maintain cholesterol homeostasis," Thummel says. "This is similar to what happens in humans who have high cholesterol levels."
Fruit flies are good for such research insights in large part because of the insects' short life span – about 30 days – meaning their development and biological processes are more easily observed than in other, longer-lived models, such as mice. Fruit flies also are easy to manipulate genetically and are less expensive to study compared to mice or other models, according to Thummel. In addition, the mechanisms by which metabolism is controlled in fruit flies are very similar to those in mice or humans.
"We can do a lot more mechanistic studies in a fly than are possible in a mouse," he says. "We can study metabolic pathways faster and more in-depth."
Along with its important role in helping to maintain proper levels of cholesterol, DHR96 also plays an integral part in regulating dietary fat metabolism, Thummel and another U of U researcher report in a Dec. 2 study in Cell Metabolism.
In flies in which DHR96 was silenced, TAG levels were markedly reduced in the intestine, making the insects resistant to diet-induced obesity. But when DHR96 was overexpressed, meaning there were higher levels of the protein, it led to increased TAG levels and made the flies more prone to being overweight. These findings show that DHR96 is required for breaking down dietary fat in the intestine of fruit flies and provide insight into how dietary fat metabolism is regulated in Drosophila.
"This nuclear receptor plays a major role in sensing and regulating cholesterol and TAG uptake in the intestine in fruit flies," Thummel says. "It functions similarly to the way LXR functions in humans, although we have a relatively poor understanding about how LXR controls these pathways."
In his future studies, Thummel intends to learn more about how DHR96 regulates metabolism by studying the functions of the genes that it controls.
Here's the abstract of the study in question:
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Horner MA, Pardee K, Liu S, King-Jones K, Lajoie G, Edwards A, Krause HM, Thummel CS. The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis. Genes Dev. 2009; 23: 2711-16. |
You gotta have heart(s) - if you're a fly, you've got 9 of them
In answer to a question about whether flies' have hearts, Associate Professor Cole Gilbert of Cornell University wrote:
Yes, flies have hearts, at least nine of them; one principal heart and eight accessory hearts. In some ways they are similar to your heart - a muscular pump that moves blood around the body. But in most ways, the hearts and open circulatory system of insects are bizarre and very different from ours.
The principal heart is a muscular tube running down the middle of the fly under the skin on top of the abdomen. The tube is closed at the back end and extends forward through the thorax to open behind the head. The tube has six slits in the abdominal portion. When the muscle relaxes, blood flows through the slits into the tube. When the muscle contracts, flaps inside the tube close over each slit and blood is forced out the front end of the tube into the head. The heart then relaxes and the tube fills with blood again. It beats like this about 370 times per minute, which is much faster than the 60 or so beats per minute of your heart.
Your circulatory system is made of closed tubes, the arteries, veins, etc, connected to the heart and other organs. In your closed system, blood pumped from the heart takes about 20 seconds to go around the body and return to the heart. The open circulatory system of insects has no direct pathway for blood pumped into the head to return to the heart. The blood simply percolates back through the body until it reaches the abdomen and enters the slits again after several minutes. This system obviously works for the fly and other insects, but it is relatively poorly designed and inefficient in many ways.
The blood of the fly carries no oxygen to its tissues, as red blood cells do in your blood. Flies get their oxygen through a different system of non-muscular tubes connected directly to the atmosphere through 22 small holes along the sides of the fly's body. When you play hard, your heart must pump faster to supply more oxygen-carrying red blood cells to your active muscles. The heart of a fly does not beat faster when it flies compared to when it is resting, because oxygen flows directly through the other set of tubes.
While the principal heart helps move blood forward, most movement of blood in insects occurs by simple sloshing around in the open system. As muscles contract to move the wings, blood is squeezed around the muscles into different body areas. Sloshing works for the main body cavity, but can't get blood into thin appendages, e.g., legs, antennae, and wings. At the base of each appendage there is an accessory heart - another small muscular pump - that moves blood through the appendage to provide muscles and nerve cells there with nutrients dissolved in the blood.
Thus, the hearts of the fly operate in a circulatory system very different from yours and mine.
As Dr Malcolm Kendrick pointed out in a email to THINCS:
"So, all in all, a pretty good model for human athersoclerotic plaque development."
So now we know: If you feed a high-fat, high-cholesterol diet to fruit flies, they become overweight and get heart disease. So that must be what happens to us, mustn't it? If you, dear reader, can think of anything more ridiculous, please email me.
By the way, has anyone ever seen an overweight fly — or a fruit fly that eats a high-fat diet?
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