Metabolomic alteration in mammary glands of pubertal mice fed a high-fat diet

Authors: Yan, Lin; RUST, BRET - Washington State University; SUNDARAM, SNEHA - Labcorp; Bukowski, Michael

Submitted to: Nutrition and Metabolic Insights
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/14/2022
Publication Date: 1/31/2023
Citation: Yan, L., Rust, B., Sundaram, S., Bukowski, M.R. 2023. Metabolomic alteration in mammary glands of pubertal mice fed a high-fat diet. Nutrition and Metabolic Insights. 16:1-10. https://doi.org/10.1177/11786388221148858.
DOI: https://doi.org/10.1177/11786388221148858

Interpretive Summary: Childhood obesity is prevalent in the U.S. and worldwide. Childhood obesity is associated with adulthood obesity. In girls, it is associated with an increased risk of breast cancer later in life. Obese girls often show early onset of puberty and early breast development with elevation of sex hormones in blood. It has been shown that consumption of the Western diet, which is rich in dietary fat, contributes to childhood obesity. We investigated whether consumption of a high-fat diet altered the metabolic profile of mammary glands in pubertal mice. We found that the high-fat diet, compared to a normal control diet, altered amino acid metabolism considerably. This is evidenced by elevations of both essential and non-essential amino acids and alteration of metabolic pathways related to protein synthesis in mammary glands. Amino acids are building blocks for protein synthesis in our body. Moreover, we found that the high-fat diet altered energy and lipid metabolism in mammary glands. Our study demonstrates that consumption of a high-fat diet disturbs metabolism in mammary glands. This disturbance may affect breast development and growth in puberty. Furthermore, findings from this study indicate the importance of a healthy diet in childhood for breast development and growth.

Technical Abstract: Childhood obesity is a risk factor for adulthood obesity and its related diseases. This study tested the hypothesis that an obesogenic high-fat diet alters the mammary metabolome in pubertal mice. We performed untargeted metabolomic analysis of primary metabolism on mammary glands from pubertal mice fed the AIN93G standard diet or a high-fat diet (HFD) for three weeks. We identified 97 metabolites for statistical comparisons. The HFD altered the amino acid metabolism considerably. This included elevated expression of branched-chain amino acids, non-essential amino acids aspartic acid and glutamic acid, and methionine sulfoxide (oxidized methionine). These changes were supported by alterations in signaling pathways related to amino acid metabolism, including the aminoacyl-tRNA biosynthesis pathway, by the HFD. Furthermore, elevations of fumaric acid and malic acid (both are intermediates of the citrate cycle) and glyceric acid (its phosphate derivatives are intermediates of glycolysis) in HFD-fed mice suggest a facilitation of both citrate cycle and glycolysis in pubertal mammary glands. Lower expression of glycerol, oleic acid, and palmitoleic acid, as well as decreased expression of genes encoding enzymes involved in lipid metabolism (Acaca, Fads1, Fasn, Scd1, and Sreb1), in HFD-fed mice indicate an attenuated lipid metabolism in pubertal mammary glands in the presence of adequate dietary fat. In conclusion, consumption of the HFD for three weeks alters metabolic profile of pubertal mammary glands. This alteration may affect mammary development and growth in pubertal mice.