A stress signal sent from fat cells to the heart could be protective against obesity-induced cardiac damage, according to new research.
This might help explain the ‘obesity paradox’, where obese individuals have better short- and medium-term cardiovascular disease prognoses compared with those who are normal weight, but have worse long-term outcomes.
“The mechanism we have identified here could be one of many that protects the heart in obesity,” said study leader Philipp E. Scherer, PhD, Professor of Internal Medicine and Cell Biology at UTSW who has long studied fat metabolism.
Study co-leader Clair Crewe, PhD, Assistant Instructor of Internal Medicine at UTSW, explained that the metabolic stress of obesity gradually makes fat tissue dysfunctional, causing shrinkage and death of its mitochondria. This unhealthy fat loses the ability to store lipids generated by excess calories in food, causing lipotoxicity and poisoning other organs. However some organs, including the heart, preemptively defend against lipotoxicity. How the heart actually senses fat’s dysfunctional state has been unknown so far.
The researchers used a genetic technique to speed the loss of mitochondrial mass and function in mice. The mice were fed a high-fat diet and became obese, and their fat cells began sending out extracellular vesicles filled with small pieces of dying mitochondria. Some of these mitochondrial snippets travelled through the bloodstream to the heart and triggered oxidative stress.
Cardiaccells produce a flood of protective antioxidant molecules to counteract this stress, and this protective backlash was so strong that when the scientists injected mice with extracellular vesicles filled with mitochondrial snippets and then induced a heart attack, the animals had significantly less damage to their hearts compared with mice that didn’t receive an injection.
Fat tissue from obese human patients showed that these cells also release mitochondria-filled extracellular vesicles.
The heart and other organs in obese individuals are eventually overwhelmed by lipotoxic effects, resulting in a number of obesity’s comorbidities. If the protective mechanism identified in this study could be artificially generated, it could result in new ways of treating obesity’s negative consequences. This might even be adapted to treat normal weight individuals.
“By better understanding the distress signal from fat,” Dr Crewe said, “we may be able to harness the mechanism to improve heart health in obese and non-obese individuals alike.”
The team’s findings were published in Cell Metabolism.
Source: UT Southwestern Medical Center
