Jeremie L. Ferey, PhD

Washington University in St. Louis (WU)

The leading cause of death in the US is heart disease, and the global problem of obesity is an important risk factor. Additionally, the offspring of overweight and obese women are more likely than those born to normal-weight women to develop cardiovascular disease as adults. Using a multigenerational model, I am testing the hypothesis that impaired cardiac function in offspring is due to a feed-forward loop in which offspring inherit damaged mitochondria that disrupt energy signaling, and propagate mitochondrial and cardiac damage. This hypothesis is founded on preliminary and published work showing that when mice (F0) were fed a high-fat/high-sucrose diet from before conception and through weaning, they gained significant weight and developed peripheral insulin resistance; their F1 progeny developed heart disease as adults; and their F1, F2, and F3 descendants had misshapen and dysfunctional mitochondria in their skeletal muscle and oocytes, despite consuming a control diet.