Maternal butyrate supplementation induces insulin resistance associated with enhanced intramuscular fat deposition in the offspring

Maternal nutrition is important for the risk of the offspring to develop insulin resistance and adiposity later in life. The study was undertaken to determine effects of maternal butyrate supplementation on lipid metabolism and insulin sensitivity in the offspring skeletal muscle. The offspring of rats, fed a control diet or a butyrate diet (1% sodium butyrate) throughout gestation and lactation, was studied at weaning and at 60 days of age. The offspring of dams fed a butyrate diet had higher HOMA-insulin resistance and impaired glucose tolerance. This was associated with elevated mRNA and protein expressions of lipogenic genes and decreased amounts of lipolytic enzyme. Simultaneously, enhanced acetylation of histone H3 lysine 9 and histone H3 lysine 27 modification on the lipogenic genes in skeletal muscle of adult offspring was observed. Higher concentration of serum insulin and intramuscular triglyceride in skeletal muscle of offspring from the butyrate group at weaning were accompanied by increasing levels of lipogenic genes and enrichment of acetylation of histone H3 lysine 27. Maternal butyrate supplementation leads to insulin resistance and ectopic lipid accumulation in skeletal muscle of offspring, indicating the importance of short chain fatty acids in the maternal diet on lipid metabolism.