How heart disease is passed on across generations

The incidence of obesity has reached alarming proportions worldwide, and increasing evidence suggests that the parents’ nutritional status may predispose their offspring to lipotoxic heart disease—the accumulation of fat in heart cells. But the mechanisms underlying the risk for intergenerational heart disease have not been clear. Researchers now show that cardiac dysfunction induced by a high-fat diet persists for two subsequent generations in fruit flies and is associated with reduced expression of two key metabolic regulators: adipose triglyceride lipase (ATGL/bmm) and transcriptional cofactor PGC-1. Increasing the expression of ATGL/bmm in the offspring of high-fat diet-fed parents protects them, and the subsequent generation, from heart lipotoxicity. The study, which was partly funded by the NHLBI and published in the journal Nature Communications, provides new perspectives for tackling the effects of metabolic syndrome across generations and preventing lipotoxic heart disease.