April 26, 2012 | 3
On the last day of Experimental Biology 2012, I had the great pleasure to be able to see the work of the Jones lab at the University of Cincinnati College of Medicine. I wrote about their work at last year’s meeting, and I’m very happy to show you all the latest advances this year!
There’s very little that’s more serious than a heart attack. Otherwise known as a myocardial infarction (MI), a heart attack is a loss of blood flow to the heart. When there isn’t enough blood flow to the heart, the heart muscles do not receive enough oxygen, and heart cells begin to die and lose their ability to pump in rhythm.
In the past, the vast majority of people who suffered from a heart attack would die. But now advances in modern medicine have enabled many people to continue for years following MI. So we are not only concerned with survival of heart attack, we are also concerned with recovery, what can help recovery and make it faster, or reduce the severity of the heart attack in the first place.
And as Haar et al, from the University of Cincinnati College of Medicine have found, sometimes what’s bad for you might not be so bad for your heart, at least, in small doses. Haar has been looking at the effects of a high-fat diet on MI outcomes in mice. She previously found that short-term high-fat diets in mice (between 24 hours and two weeks of exposure, but not longer, otherwise you get some very fat mice), produced protection during a heart attack. When she induced an experimental heart attack in mice, mice that had been treated with a high fat diet for a short period of time showed reduced damage when compared to control mice. Haar also showed that 24 hours worth of high-fat diet produces protection for about 24 hours afterward, but not 48 hours (a double cheeseburger every other day, then?).
All this is well and good, but the important question is asking how does this protection work? Haar and her colleagues hypothesize that a high-fat diet can shift the damage balance in the heart from apoptosis (cell death) to autophagy (a shifting of cellular energy resources), and they hypothesize that an important molecule involved is NF-kappaB.
NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells), is a protein complex which affects the transcription of DNA, and could have widespread effects on how cells function under stress. To examine the role of NF-kappaB in the high-fat protection from MI, Haar took a group of dominant-negative mice, animals which specifically fail to activate NF-kappaB in the heart. She fed some of them on a high-fat diet, gave them all a heart attack, and looked to see if the protective effects of the high-fat diet were still present. In the NF-kappaB dominant negative mice, the injury size following MI was larger, and the high-fat diet failed to protect the mice from the effects.
But NF-kappaB affects a lot of genes, what specifically was going on? It appears that the heart cells are not dying at the same rates in mice on a high-fat diet, Haar saw fewer markers of apoptosis in the high-fat group. To see if the cells were instead undergoing autophagy, she looked at the marker Beclin-1. Beclin-1 is a marker for autophagy, a way to show that cells are reallocating their resources to preserve function, rather than dying in response to the severe stress of the MI. And it turns out that a high-fat diet increases the expression of Beclin-1 in the damage zone of mice having a heart attack. Not only that, this increase is blunted in the dominant negative NF-kappaB mice following heart attack, showing that NF-kappaB may be controlling the increase of Beclin-1. This means that high-fat diets are shifting the balance of the heart from apoptosis to autophagy, allowing the heart to suffer less damage during heart attack.
Of course, it’s not a good idea to go eat a double-cheeseburger in perfect comfort. After all, people who habitually eat high fat diets are at a much greater risk for heart attack in the first place. But it’s an interesting look into how the heart can protect itself, and may mean new potentials for treatment in those who suffer heart attack. And maybe you don’t have to feel quite so guilty about the high-fat food, if you only have it once in a while.