What damage does obesity cause to the heart?
Obesity causes an increase in the stiffness of the heart, making it hard for the heart muscle to relax and fill with blood in between heartbeats. This abnormal stiffness can lead to congestive heart failure and other problems as it becomes more severe.
Obesity also increases the risk of coronary artery disease and heart attacks, although that was not the focus of this study. Obesity causes an increase in inflammation in the body, which is also known to increase cardiac risk.
Was it previously thought possible to reverse this heart damage through weight loss?
Yes. Weight loss improves heart contractile function as well as the relaxing function. It also helps reduce abnormal thickening of the heart muscle and improve congestive heart failure.
The new finding of this study is that the benefits were much greater in younger mice than in the older mice.
What did your research into weight loss and heart damage involve?
We studied two groups of genetically obese mice, a younger group and an older group. Both younger and older mice were found to have heart damage similar to the type found in humans.
We put all mice on a calorie-restricted diet, and both groups lost a similar amount of weight. Our goal was to see if weight loss would reverse the damage in one or both groups. We were most interested in testing whether the heart stiffness would improve.
How did you genetically engineer mice to be obese?
The mice were originally made by deleting a part of the gene for the hormone leptin, which helps regulate metabolism and triggers a sense of feeling “full”. However, we did not engineer these mice ourselves. They are commercially available from Jackson Laboratories for research purposes.
What did your research find?
We found that in the younger mice, the heart stiffness returned to normal after weight loss, but in the older mice, the stiffness did not improve.
Some other factors, such as the amount of oxidative stress, or free radical damage, improved with weight loss in both groups.
Why do you think some factors improved with weight loss in both groups but not heart stiffness?
Heart stiffness is partly due to microscopic fibrous tissue and scarring in the heart. Once that has been present for a long time, it eventually becomes irreversible.
The level of oxidative stress improved in both groups because the factors contributing to that type of damage change more readily. Also the damage can often be reduced by natural repair mechanisms within the cells if the oxidative stress level goes down.
Do you think your results would have been different if the mice had lost weight through exercise rather than a calorie-restricted diet?
That’s a great question that we are definitely interested in studying next. We know there are many benefits of exercise in general; including improvements in heart function and heart efficiency, and lowering oxidative stress and inflammation levels.
We don’t know the answer in this model yet, but perhaps using exercise to lose weight, either by itself or in combination with calorie restriction, would have an even greater benefit. It is even possible that it could restore the weight loss benefit in the older animals, but we need to do another study to find out for sure.
In humans, exercise also lowers blood pressure, improves diabetes, and improves mood, so I recommend it to all my patients.
Was there an incremental negative correlation between age of weight loss and ability to reverse heart damage or did your research find more of a step change once the mice were above a certain age?
We only studied two different age groups, so a more extensive study would be needed to determine the true answer to this question. My opinion is that it is probably incremental, but we haven’t tested that yet.
Did your research reveal the mechanism by which heart damage becomes irreversible?
We do not yet know the exact mechanism, but we have some clues that it may be related to abnormal fat droplet storage or inflammation. Again, further study is needed to determine the answer.
Abnormal fat droplet storage and inflammation can both lead to increased oxidative stress, which we know is harmful. Although oxidative stress itself was reversible in this study, the damage it leaves behind was not.
We believe it is the duration of obesity, and this, duration of exposure to these harmful factor, that eventually leads to microscopic scarring and abnormal heart muscle stiffness, among other problems.
Do you think these findings would be applicable to humans?
I think it is quite likely that the findings would be applicable to humans, although would have to do a study in people first before drawing any definite conclusions.
Are there plans to carry out research into the impact of weight loss on heart damage in humans?
Not in my own laboratory, but some of my colleagues and other groups around the world are looking into it.
People who undergo bariatric surgery or those who are involved in intensive weight loss programs may be good groups to study since differences would probably be easier to detect if there is a large amount of weight loss.
What advice would you give people who are obese in the meantime?
It’s never too late to work on reducing your cardiovascular risk, but it’s best to start as soon as possible to get the greatest benefit. Eat a heart healthy diet, exercise regularly, don’t smoke, and work toward a healthy body weight in a sensible way.
Where can readers find more information?
The original article is published in Journal of Cardiovascular Translational Research and is currently available online. It will appear in print within the next couple of months. http://link.springer.com/article/10.1007%2Fs12265-013-9453-4
The press release from Johns Hopkins University is available here:
http://www.hopkinsmedicine.org/news/media/releases/losing_weight_sooner_rather_than_later_gives_the_best_chance_of_reversing_heart_damage_from_obesity_according_to_study
About Dr Lili Barouch
Dr. Barouch is currently Assistant Professor of Medicine in the Division of Cardiology at the Johns Hopkins University School of Medicine.
Dr. Barouch received her undergraduate degree from Harvard University in 1992 and her medical degree from Johns Hopkins in 1996. She continued at Johns Hopkins for residency training in Internal Medicine, completed in 1999, and fellowship in Cardiovascular Disease and Advanced Heart Failure/Transplant, completed in 2003.
Dr. Barouch has a longstanding interest in obesity and heart disease, as well as women’s cardiovascular health. She has specific expertise in peripartum cardiomyopathy, heart disease after breast cancer treatment, and the role of obesity in the development of heart failure.
She has been a member of the cardiology faculty at Johns Hopkins since 2003 and has performed extensive independent research within the Cardiovascular Division.
Immune dysfunction mechanism discovered in stroke and heart attack patients