Abstract
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.
Highlights
Maternal nutrition during gestation and lactation has profound effects on fetal growth and development with lifelong consequences [1, 2]
The body weight and gastrocnemius muscle weight (GW) (P < 0.01) of adult offspring were significantly enhanced in the butyrate group compared with control (Table 1), though both of them showed no obvious differences at weaning age
When adult offspring were challenged with a glucose tolerance test (GTT) and an insulin tolerance test (ITT), butyrate group rats showed permanently increased serum glucose levels (Figure 1a, 1b), indicating decreased responsiveness as a sign for development of insulin resistance
Summary
Maternal nutrition during gestation and lactation has profound effects on fetal growth and development with lifelong consequences [1, 2]. Animal models confirm that maternal diet influences the development of insulin resistance and adiposity in the offspring [3, 4]. It has been shown that nutritional factors during offspring early life possibly influence permanently the risk of an individual to develop insulin resistance in adulthood [6, 7]. Butyrate is a SCFA which is produced in the gastrointestinal tract [9], and acts as an energy source to meet energy requirements in ruminants and monogastric animals [10, 11]. A previous study suggested maternal high fiber diet, which could produce butyrate by microbial fermentation in the gastrointestinal tract, increased the expressions of CCAAT/enhancer-binding protein (C/EBP) and peroxisome proliferator-activated receptor γ (PPARγ) related to adipogenesis [16]. Radunz et al [17] found that progeny from dams fed high fiber diet had increased intramuscular fat deposition and diminished www.impactjournals.com/oncotarget
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