Anti-aging target SIRT1 protects newborns from the effects of maternal obesity

Obesity is well-known as a global health concern. Obesity before and during pregnancy can significantly affect both the mothers and their babies' health. Particularly, maternal obesity can lead to fetal overgrowth, primarily contributing to the development of obesity and associated diseases such as diabetes, liver and kidney diseases later in life. Unfortunately, the mechanisms underlying such transmissible effects are still unclear. On the other hand, lifestyle intervention trials to manage gestational weight gain through diets, physical activities and behavioural modification techniques have achieved modest success in improving the babies' health outcomes. As such, investigation of alternative approaches to mitigate the effects of maternal obesity across generations has become imperative. Sirtuin (SIRT)1 is a potent regulator of cell growth, metabolism and stress responses, and one of the most appealing targets for aging and weight gain related disorders. In obesity, SIRT1 activity is significantly suppressed in multiple organs such as liver and fat tissues. Increasing the expression and/or reactivation of SIRT1 has been shown to be of particularly beneficial against obesity-associated comorbidities. The effects of such therapeutic approaches on the offspring of obese mothers, which were largely unknown, has been the focus of my research. To investigate the topic, we made female mice become obese by feeding them a high-fat diet before and during pregnancy and used genetically modified mice with increased levels of SIRT1. We looked at various tissues from brain to fat tissue and liver to understand the systemic reactions of the body. We also compared the effects when the intervention was on the offspring themselves or their mothers or fathers. The results not only suggest SIRT1 can indeed be used as a target for managing the effects of maternal obesity on the offspring but also specify newborns as the superior subject compared to mothers and fathers for the intervention.