Fat cell distress signal could help unlock the "obesity paradox"
Obesity is associated with a whole range of health problems, but in some specific cases, it appears to be protective in the short term against cardiovascular disease. This “obesity paradox” remains mysterious, but now researchers may have uncovered one possible mechanism behind it.
Normally, fat tissue stores excess calories as lipids, but over time metabolic stress can cause this tissue to become dysfunctional. That means lipids are more likely to build up in organs such as the heart, liver or kidneys, causing a condition known as lipotoxicity that can bring a variety of health problems. But strangely enough, lipotoxicity doesn’t have a clear-cut correlation with obesity – in fact, some argue that obesity can actually protect against that damage, at least for a little while.
In several studies in the early 2000s, scientists noticed something unexpected. Among patients with chronic kidney disease undergoing hemodialysis, those who were overweight or obese had higher survival rates than those with a healthy weight. This became known as the obesity paradox, and now, researchers at the University of Texas Southwestern Medical Center have discovered one mechanism that may help explain what’s going on.
The team tested the phenomenon in mice that had been engineered so that their fat tissue became dysfunctional faster, then fed them a high-fat diet. It seems that the fat cells give off a “distress signal” as they become dysfunctional, which the heart responds to with a powerful and lasting defense.
A marker of dysfunctional fat tissue is that the mitochondria – the energy-producing structures inside cells – shrink and die off, and the researchers found that fragments of these dying mitochondria were being released into the animals’ bloodstream. Once they reached the heart, they triggered oxidative stress, which can damage organs. In response, heart cells produce antioxidant molecules to protect the organ.
That protection is surprisingly strong, and may play a role in the obesity paradox. The team tested just how strong it may be by injecting mice with molecules containing more of the dying mitochondrial snippets, then inducing a heart attack. And sure enough, the mice that had received the injections had significantly less damage to the organ than mice that didn’t get the injection.
“The mechanism we have identified here could be one of many that protects the heart in obesity,” says Philipp Scherer, lead author of the study.
Follow-up tests looked for signs of this process in human patients. The team examined fat tissue samples taken from obese patients, and found that they also were giving off particles containing dying mitochondria. That suggests that not only could this help at least partly explain the obesity paradox, but it could potentially be adapted into a preventative treatment against heart damage.
“By better understanding the distress signal from fat, we may be able to harness the mechanism to improve heart health in obese and non-obese individuals alike,” says Dr. Clair Crewe, co-lead author of the study.
The research was published in the journal Cell Metabolism.
Source: University of Texas Southwestern