β-Carotene Impacts the Liver MicroRNA Profile in a Sex-Specific Manner in Mouse Offspring of Western Diet-Fed Mothers: Results from Microarray Analysis by Direct Hybridization

• Published in: International journal of molecular sciences 2024-12, Vol.25 (23), p.12899
• Main Authors: Abrego-Guandique, Diana Marisol, Galmés, Sebastià, García-Rodríguez, Adrián, Cannataro, Roberto, Caroleo, Maria Cristina, Ribot, Joan, Bonet, Maria Luisa, Cione, Erika
• Format: Article
• Language: English
• Subjects: Animals; beta Carotene - metabolism; Body fat; Cancer; Carotenoids; Diet; Diet, Western - adverse effects; Dietary Supplements; DNA methylation; DNA microarrays; Enzymes; Epigenetic inheritance; Female; Females; Gene Expression Profiling; Genes; Insulin resistance; Kinases; Liver; Liver - metabolism; Male; Males; Metabolism; Mice; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Physiological aspects; Pregnancy; Prenatal Exposure Delayed Effects - genetics; Prenatal Exposure Delayed Effects - metabolism; Sex Factors; Sexes; Triglycerides; Vitamin A
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms252312899

Maternal unbalanced diets cause adverse metabolic programming and affect the offspring's liver microRNA (miRNA) profile. The liver is a site of β-carotene (BC) metabolism and a target of BC action. We studied the interaction of maternal Western diet (WD) and early-life BC supplementation on the epigenetic remodeling of offspring's liver microRNAs. Mouse offspring of WD-fed mothers were given a daily placebo (controls) or BC during suckling. Biometric parameters and liver miRNAome by microarray hybridization were analyzed in newly weaned animals. BC sex-dependently impacted the liver triacylglycerol content. The liver miRNAome was also differently affected in male and female offspring, with no overlap in differentially expressed (DE) miRNAs between sexes and more impact in females. Bioinformatic analysis of DE miRNA predicted target genes revealed enrichment in biological processes/pathways related to metabolic processes, regulation of developmental growth and circadian rhythm, liver homeostasis and metabolism, insulin resistance, and neurodegeneration, among others, with differences between sexes. Fifty-five percent of the overlapping target genes in both sexes identified were targeted by DE miRNAs changed in opposite directions in males and females. The results identify sex-dependent responses of the liver miRNA expression profile to BC supplementation during suckling and may sustain further investigations regarding the long-term impact of early postnatal life BC supplementation on top of an unbalanced maternal diet.