Experimental Biology Blogging: High Fat Diets and Cardio Protection in Mice

Apr 13 2011 Published by under Experimental Biology Blogging 2011

Heart failure and heart attacks (otherwise known as myocardial infarction) are some seriously scary problems. Myocardial infarction in particular seems to strike without warning, leading either to death or to months of recovery and reduced quality of life. So not only are scientists working on what can help people recovering from heart attacks or living with heart failure, they also want to look at what might protect people who are in danger of cardiac disease.

There's a lot of seemingly paradoxical findings on what can help with cardiac disease. Sometimes people with high cholesterol seem to be protected. Sometimes people on caloric restriction seem to be protected. While the findings seem to be opposites, it's possible that similar physiological mechanisms could be involved (or different ones, that’s possible too).

So how do you find out what changes might protect against MI? One way is to feed a bunch of mice some delicious high fat diets!

Haar et al. "Acute high fat feeding influences cardiac function and confers cardio protection against ischemic injury" University of Cincinnati College of Medicine, presented at Experimental Biology, 2011.

Too look at possible protective effects of a high fat diet on myocardial infarction in mice, Haar et al fed groups of mice high fat diets (60% fat) for 24 hours, 1 week, 2 weeks, or 6 weeks. This high fat diet, if you feed mice on it for 8 weeks, will produce obesity and the problems associated with in mice, but for 24 hours, 1 week, or 2 weeks, doesn't produce a change in weight. After this high fat diet, the scientists expected to see an increase in cholesterol (after all, they were eating a ton of fat!), but surprisingly they failed to see anything there. They DID, however, see a decrease in serum fatty acids and triglycerides after two weeks of a high fat diet.

The rationale for the study was the evidence that high fat diet and high serum cholesterol correlates with protection against cardiac damage in some human studies; the scientists thought that perhaps an increase in nonessential free fatty acids from fats, the main source of energy for the heart, might mirror, in the mice, the protection reported in humans.

After the mice had the diet for 1 day, 1 week, or 2 weeks, Haar et al induced an MI to create a 26% infarct of the ventricular tissue by blocking the blood flow to a part of the heart temporarily, mimicking a heart attack.

They found that mice that had been fed with a high fat diet for 24 hours, 1 week, or 2 weeks got a significant protection against the damage caused by the MI. However, the protection is lost in mice that were fed the high fat diet for 6 weeks. Seeing that the hearts looked as though they were protected, the scientists looked at functional studies, and found that the mice on the high fat diets showed better ejection fraction (an indication of improved heart function), than mice on control diets who had had an MI.

You might think "hey! High fat diets protect from heart attack! ICE CREAM FOREVAR!!!" But it's just not that simple. After all six weeks of the high fat diet produces no protection at all and in fact produces problems. It looks like only up to two weeks of a high fat diet is protective. But the question now is, how long does that protection LAST?

It turns out, not long at all. Haar et al looked at effects of myocardial infarction in mice who had been fed the high fat diet for 24 hours. Immediately after the diet, the mice were protected. But a day after the diet, the protection was less, and 48 hours afterward, all protection produced by the high fat diet was gone, indicating that the changes produced by high fat diets are very short lived (though the effects of 1 and 2 week treatments still remain to be examined).

So we know that we have a short lived protection induced by a high fat diet. But what is the mechanism? The authors of this study chose to look at NF Kappa B, a protein that controls the transcription of DNA and which has been known previously to mediate the results of a protective cardiac treatment called ischemic preconditioning. This is a technique when you induce small ischemic injuries in order to produce protection from a large scale MI. The scientists wanted to know if this small injury mechanism and the high fat diet had something in common. They used mice that had a non-functional copy of NF kappa B, and found that high fat feeding those mice was no help at all, they had no protections. So it looks like NF kappa B is required for the protections induced by this high fat diet. Current research efforts are directed at understanding more details of this mechanism, and why it is reversed in longer high fat feeding.

So they are on their way to a mechanism for how high fat diet might help to protect against cardiac injury. But we are a LONG way from taking this to a clinic. After all, long term high fat diets are no good for you at all. So rather than stocking up on large blocks of brie (though it might be delicious), it's probably best to wait until we have a final mechanism for what can help with cardiac protection. Once the mechanism is understood, new therapeutic targets may be identified that can be used to harness the protection and/or prevent the inactivation of the protection long-term.

4 responses so far

  • aek says:

    I'm in literal awe of all that you are blogging! I don't know how you are doing it all and are able to explain so many varied disciplines' research so winningly, but I'm grateful that you do!

    I've got a confounder question about this study: what were the fat sources (eg sat, mono, O6:O3 ratio and absolute values) and what were the carbohydrates used in the control and study diets? Was the protein % and sourcing the same in both diets?

    I have a suspicion that carbs factor in this study, as well as fat sources. That's one of te problems with nutrition studies - so many darned variables to control.

    Did the researcher investigate using a Paleo/carb restricted diet, or was this a fat/carb combo meal based diet is what I'm asking? Obviously the super sizing is a factor.

    Keep 'em coming, but have some fun, too!

    Thanks, Sci!

    • scicurious says:

      Protein % and sourcing were the same, the diets were purchased research diets that are balanced in this regard. The exact carbs I don't know, but I presume those in the control and chow diets were the same. It's actually not a paleo/carb kind of thing vs fat/carb, though the diet used was mostly certainly further on the fat end. The diet used is one that, at the 6 week time point, induces obesity in mice and is used to study diet-induced obesity.

  • becca says:

    AHHHHHHHHHHHHHHHHHHHHHHHH
    NF-kB
    So are you basically inducing an inflammatory state?
    I wonder how this ties into the work with TLR ligands and building tolerance to some insults vs. sensitizing to other insults. It seems like NF-kB is set up to respond to such a diverse array of stuff, in such a dynamic fashion (e.g. short term activation achieving very different effects than long term activation) that it's an exercise in futility to predict how it's working a priori.
    Were the mice in question nfkb1-/- (i.e. p50/p105) knockouts? Because the loss of p105 in addition to p50 certainly complicates the analysis. I presumed they also show p50 in the nucleus of cells (and what kind of cells, specifically, and how is the fat being sensed)?

    • scicurious says:

      Yeah, as far as I can tell they are basically inducing a small inflammatory state as protective against a large injury. But it's not my field.

      The mice were NOT the nfkb1-/-. They were knockdowns of a different lineage, I'm pretty sure, though I'd have to ask to be specific.