Preventive and Ameliorative Effects of Alanine Supplementation on High-Fat Diet–Induced Obesity and Metabolic Dysfunction via the Gut–Liver–Adipose Axis in C57BL/6J Mice

The present study aimed to investigate the role of alanine (Ala) in regulating obesity and glucose homeostasis in C57BL/6J mice. Two independent experiments were conducted: a preventive model (Experiment 1: 10 weeks of concurrent high-fat diet (HFD) and Ala administration) and a therapeutic model (Experiment 2: 10 weeks of Ala treatment following a 10-week HFD-induced obesity period). In Experiment 1, Ala significantly attenuated HFD-induced weight gain (35.16 g vs. 30.82 g, <i>p</i> < 0.001), improved serum biochemistry profiles, and downregulated the expression of inflammatory proteins (<i>p</i> < 0.05). In Experiment 2, Ala administration reduced white adipose tissue (WAT) mass (1.82 g vs. 1.15 g, <i>p</i> < 0.001) and improved glucose tolerance (<i>p</i> < 0.05). The above benefits were validated by experimental analysis. Microbiota analysis from Experiment 1 suggested that changes in the relative abundance of <i>Acinetobacter</i>, <i>Lachnospiraceae_NK4A136_group</i>, and <i>Haemophilus</i> could serve as a potential indicator of species associated with obesity prevention. Taken together, the above findings suggest that Ala has the potential to prevent and treat obesity through the gut-liver-adipose axis.