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

Area of Science:

• Metabolic disease research
• Developmental programming
• Hepatic steatosis

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health concern.
• Early-life nutrition significantly impacts long-term metabolic health.
• Maternal overnutrition during lactation can predispose offspring to metabolic disorders.

Purpose of the Study:

• To investigate the impact of a lactational Western-style fat diet on male offspring's metabolic health.
• To determine if this exposure programs offspring for adult-onset metabolic dysfunction and MASLD.
• To assess the role of lipid metabolism alterations in diet-induced MASLD.

Main Methods:

• Dams were fed either a standard chow or Western-style fat diet during lactation (21 days).
• Offspring were fed standard chow post-weaning until 3 months of age.
• Adult offspring were challenged with a high-fat diet to assess metabolic and hepatic responses.

Main Results:

• Lactational Western-style fat diet exposure increased offspring susceptibility to weight gain, obesity, and insulin resistance in adulthood.
• Offspring exhibited hepatomegaly and hepatic triglyceride accumulation, indicative of MASLD.
• Altered lipid metabolism pathways may mediate these diet-induced hepatic changes.

Conclusions:

• Neonatal exposure to a Western-style fat diet can program male offspring for MASLD.
• This early-life dietary insult primes the liver for metabolic dysfunction later in life.
• Findings highlight the critical role of maternal diet during lactation in metabolic disease prevention.