Organ-Specific Transcriptional and Metabolic Remodelling During Late Mouse Adolescence

These transcriptional changes correspond to a coherent metabolic maturation driven by the gut-liver axis. Intestinal maturation enhances lipid absorption and microbial fermentation, leading to increased circulating levels of short-chain fatty acids, poly-unsaturated glycerolipids, and sphingomyelins. Elevated hepatic production of ketone bodies, driven by up-regulated fatty acid metabolism genes, provides an efficient alternative energy substrate for peripheral tissues like the heart.

Urinary metabolite profiles, marked by increased acylglycines and tricarboxylic acid (TCA) cycle intermediates, further confirm heightened mitochondrial energy turnover and fatty acid beta-oxidation. Collectively, this coordinated maturation from 8 to 12 weeks signifies the transition from a highly plastic developmental state to a stable, energy-efficient, and metabolically flexible adult phenotype.