Maternal Separation Differentially Programs Structural and Functional Remodeling of Visceral Adipose Tissue Depots in Mice Exposed to a Post-Weaning High-Fat Diet

Visceral adipose tissue (VAT) is a metabolically active organ that undergoes structural and functional remodeling under obesogenic conditions. Early-life stress, such as maternal separation (MS), may modulate these processes, but its depot-specific effects remain poorly characterized. This study aimed to determine whether MS modulates VAT remodeling in response to post-weaning high-fat diet (HFD) exposure in male C57BL/6 mice. Animals underwent MS during the early postnatal period (PND2–16) or remained unmanipulated (UM), and were subsequently fed either a control diet (CD) or an HFD for 16 weeks (groups: UM-CD, UM-HFD, MS-CD, MS-HFD). Visceral adipose tissue was collected and analyzed at PND133. Perigonadal (PGAT), retroperitoneal (RPAT), and mesenteric (MSAT) visceral adipose tissue deposits were analyzed by histology, Picrosirius Red staining, and immunohistochemistry for leptin and UCP-1; apoptosis was assessed by TUNEL assay. HFD induced adipocyte hypertrophy and early inflammatory changes, while MS predominantly affected stromal organization. Collagen remodeling was depot-specific: PGAT showed an adaptive pattern, RPAT exhibited a significant MS×HFD interaction, and MSAT was primarily affected by MS regardless of diet. Leptin immunoreactivity increased with HFD in UM animals but was attenuated in MS mice, particularly in MSAT. UCP-1 signal was low and heterogeneous, without clear morphological browning. Apoptosis increased in MSAT under MS-HFD conditions. These findings indicate that early-life stress programs depot-specific VAT remodeling, with MSAT emerging as particularly susceptible to obesogenic challenge.