Abstract
OBJECTIVE: We investigated how a maternal Western diet (WD) affects milk microRNA (miRNA) profile and associates with metabolic programming in adipose tissues in pups. We also explored the impact of betaine supplementation during suckling, as betaine levels are reported to be reduced in WD-fed dams' milk. METHODS: A microarray analysis was performed to profile miRNA expression in dams' milk. Betaine levels were measured in the milk of dams and the plasma of their offspring. We also analyzed the expression of miRNA target genes in white and brown adipose tissues through gene expression analysis. RESULTS: Our findings confirm decreased betaine levels in the milk of WD-fed dams and the plasma of their offspring. The miRNA screening identified 37 deregulated miRNAs (36 downregulated), with the following 6 as the most relevant: miR-223-3p; miR-32-5p; let-7i-5p; miR-140-5p; miR-29a-3p; and miR-29c-3p (downregulated). Some of their target genes were upregulated in brown and white adipose tissues, particularly those related to thermogenesis and browning. Betaine supplementation in pups demonstrated a slight protective effect in females by enhancing thermogenic capacity. CONCLUSIONS: Our results underscore the profound impact of a maternal WD on milk miRNA composition, potentially influencing gene expression, thermogenesis, and adiposity in the offspring, with sex-related differences.