Lactational Western-Style Fat Exposure in Mice Programs Metabolic Dysfunction-Associated Steatotic Liver Disease...

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of liver disease. Early-life exposure to maternal overnutrition during critical developmental windows, such as lactation, can predispose offspring to develop metabolic disease. We previously demonstrated that consumption of a high fat diet (60% fat) during lactation leads to the development of insulin resistance and MASLD in male offspring. However, no studies have investigated the role of a lactational Western-style fat (45% fat) exposure, which is more clinically relevant and representative of human food consumption habits. Dams were fed either a standard chow or Western-style fat diet from delivery through the 21-day lactation period. At weaning, all offspring were fed standard chow until 3 months of age, when a subset from each group was challenged with an additional high-fat stressor. Exposure to a Western-style fat diet during lactation increased male offspring susceptibility to weight gain, obesity, and insulin resistance when fed a high fat diet in adulthood. Furthermore, these offspring demonstrated hepatomegaly and hepatic triglyceride accumulation, which may be mediated by altered lipid metabolism. These findings indicate that an indirect neonatal exposure to a Western-style fat diet can program male offspring to develop MASLD later in life.