Yan Lin, Rust Bret M, Sundaram Sneha, Bukowski Michael R
U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND, USA.
Nutr Metab Insights. 2023 Jan 31;16:11786388221148858. doi: 10.1177/11786388221148858. eCollection 2023.
Dietary malpractice is a risk factor for obesity. This study tested the hypothesis that consumption of a high-fat diet alters 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 3 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) and an alteration in the aminoacyl-tRNA biosynthesis pathway. Furthermore, elevations of fumaric acid and malic acid (both are citrate cycle intermediates) and glyceric acid (its phosphate derivatives are intermediates of glycolysis) in HFD-fed mice suggest an acceleration of both citrate cycle and glycolysis. Lower expression of glycerol, oleic acid, and palmitoleic acid, as well as decreased mammary expression of genes encoding lipid metabolism (, , , , and ) in HFD-fed mice indicate an attenuated lipid metabolism in the presence of adequate dietary fat. In conclusion, consumption of the HFD for 3 weeks alters metabolic profile of pubertal mammary glands. This alteration may affect mammary development and growth in pubertal mice.
饮食不当是肥胖的一个风险因素。本研究检验了以下假设：食用高脂饮食会改变青春期小鼠的乳腺代谢组。我们对喂食AIN93G标准饮食或高脂饮食（HFD）3周的青春期小鼠的乳腺进行了初级代谢的非靶向代谢组学分析。我们鉴定出97种用于统计比较的代谢物。高脂饮食显著改变了氨基酸代谢。这包括支链氨基酸、非必需氨基酸（天冬氨酸和谷氨酸）以及甲硫氨酸亚砜（氧化型甲硫氨酸）的表达升高，以及氨酰-tRNA生物合成途径的改变。此外，喂食高脂饮食的小鼠中富马酸和苹果酸（两者均为柠檬酸循环中间体）以及甘油酸（其磷酸衍生物是糖酵解中间体）的升高表明柠檬酸循环和糖酵解均加速。喂食高脂饮食的小鼠中甘油、油酸和棕榈油酸的表达降低，以及乳腺中编码脂质代谢的基因（、、、和）的表达降低，表明在饮食脂肪充足的情况下脂质代谢减弱。总之，喂食高脂饮食3周会改变青春期乳腺的代谢谱。这种改变可能会影响青春期小鼠的乳腺发育和生长。
