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Brown adipose tissue (BAT) is a crucial regulator in energy expenditure by dissipating energy in the form of heat through mitochondrial uncoupling protein 1 (UCP1). Previously, we demonstrated that n-3 PUFA (Omega-3 Polyunsaturated Fatty Acids) increase brown adipogenesis by miRNA-mediated epigenetic mechanisms. Given that BAT is formed at the late stage of pregnancy, we hypothesized prenatal exposure of n-3 PUFA through maternal nutrition potentiates BAT development. To test this hypothesis, Female C57BL/6 mice were fed a diet containing n-3 PUFA (3%) derived from fish oil (FO), or an isocaloric diet devoid of n-3 PUFA (Cont), and same diet was maintained throughout the pregnancy and lactation. Results showed that maternal FO was effectively delivered to the offspring significantly reducing n-6/n-3 ratio, altered blood lipid profile, and upregulated brown adipose tissue specific genes and proteins. The elevated levels of brown adipose tissue signature gene profiles, i.e., Uncoupling protein 1 (UCP1), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), in weaned pups with maternal FO intake were correlated with higher expression of GPR120 and the functional cluster of brown-specific miRNAs including miR30b and miR193b/365. Intriguingly, augmented BAT development in offspring by maternal FO intake was also associated with 1) increased epigenetic marks at H3K27Ac and H3K9me2, and decreased histone deacetylase 1 (HDAC1), and 2) upregulation of Drosha, which is a miRNA-editing enzyme for pre-miRNA production. More importantly, benefits of maternal FO intake remained later in life showing that pups that received maternal FO presented a lower body weight at weaning, an increase in energy expenditure and higher core body temperature against acute cold exposure in later life. Taken together, our results indicated that prenatal exposure to n-3 PUFA potentiates the offspring’s BAT development, at least partly via synergistic epigenetic modifications in histone modifications and miRNA production, which may confer long-lasting metabolic benefits to offspring.
Advisor: Soonkyu Chung