NOV 24, 2021 6:33 AM PST

Stressed Mitochondria From Fat Cells Are a Warning to the Heart

WRITTEN BY: Carmen Leitch

While obesity is closely linked to cardiovascular disease, that connection is murky. Some people who are considered obese have better short and intermediate cardiovascular disease outcomes compared to lean individuals, though their long-term prognoses are usually worse. A recent study reported in Cell Metabolism may help explain that so-called obesity paradox.

Image shows heart cells that have taken up red colored fat cell-derived extracellular vesicles. / Credit  UT Southwestern Medical Center

When obesity occurs, the energy-generating organelles called mitochondria in fat cells get stressed, they lose mass, and their function is disrupted. The mouse model in this study was genetically engineered to lose mitochondrial mass quickly, and then fed a high-fat diet so they would gain weight. When this mitochondrial stress occurred, the fat cells responded by releasing a significant amount of small extracellular vesicles (sEVs), little sacs that can ferry cargo to different tissues.

In this case, the cargo the sEVs carried was bits of mitochondria that were released into the bloodstream. That led to a sequence of events that triggers antioxidant signaling in the heart. The cells were temporarily protected from oxidative stress.

"The mechanism we have identified here could be one of many that protects the heart in obesity," said study leader Philipp E. Scherer, PhD, a Professor of Internal Medicine and Cell Biology at the University of Texas Southwestern (UTSW).

Obesity leads to metabolic stress, which causes fat tissue to become dysfunctional over time. The mitochondria in that tissue get small and begin to die, and this unhealthy fat eventually can't store the excess lipids that come from excess food consumption. This causes lipotoxicity, and organs get poisoned, explained study co-leader Clair Crewe, Ph.D., an Assistant Instructor of Internal Medicine at UTSW.

But it seems that some organs, like the heart, can defend themselves against lipotoxicity. This study has revealed how cells in those organs might be able to sense lipotoxicity so they can repsond. It's not known how long organs can continue to use that defense, but they are eventually overwhelmed, added Crewe.

When the researchers followed up on these findings in people, they found that obese patients had cells that released vesicles containing mitochondria, which suggested this mechanism is also true in humans. This study could help researchers find ways to bolster those protective mechanisms.

"By better understanding the distress signal from fat," Crewe said, "we may be able to harness the mechanism to improve heart health in obese and non-obese individuals alike."

Sources: UTSW Medical Center, Cell Metabolism

About the Author
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Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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