Mommy issues: how maternal diet shapes offspring mitochondrial physiology
Abstract Exposure to early life stressors, including maternal obesity and the consumption of a calorically dense diet, during critical windows of fetal development is associated with an elevated and earlier risk of developing childhood obesity, type 2 diabetes, and other cardiometabolic diseases. As mitochondria lie at the intersection of energy metabolism and cellular stress response, alteration in their function is a likely mediator of the observed effects of maternal diet quality on offspring cardiometabolic health. This review summarizes the effect of a maternal high-calorie diet on offspring mitochondrial content, architecture, and bioenergetics in skeletal and cardiac muscle, comparing these findings across various animal models used to study developmental programming. How alterations in these mitochondrial properties influence substrate dependence, oxidative capacity, and metabolic efficiency and contribute to impaired metabolic flexibility and cardiometabolic risk are highlighted. Finally, insights into potential mechanisms, such as redox imbalance, disrupted mitochondrial-nuclear communication, and epigenetic remodeling, linking maternal diet to changes in mitochondrial homeostasis are discussed. Understanding how these early alterations in mitochondrial physiology predispose offspring to increased cardiometabolic disease risk may reveal novel therapeutic interventions.