Javiera Navarrete

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.

The proposed research aims to evaluate the histopathological effects of the intra-articular administration of recombinant human proteoglycan 4 (rhPRG4) on an experimental model of induced temporomandibular joint (TMJ) osteoarthritis (OA) in rabbits. An experimental study was conducted on rabbit TMJs. Twenty-four TMJs were included, distributed as follows: (1) TMJ-C, a control group consisting of four healthy TMJs; (2) TMJ-OA, a group consisting of five TMJs with OA; (3) TMJ-OA-WT, a group consisting of five untreated TMJ-OAs; (4) rhPRG4-30, a group consisting of five TMJ-OAs treated with rhPRG4 30 μg/mL; and (5) rhPRG4-100, a group consisting of five TMJ-OAs treated with rhPRG4 100 μg/mL. A histopathological analysis was performed, considering the mandibular condyle, articular disc, and mandibular fossa, comparing the groups. In addition, a quantitative comparative analysis was performed using the Osteoarthritis Research Society International (OARSI) scale. Kruskal–Wallis and Dunn’s post hoc tests were used for statistical analysis, considering a statistical significance of p < 0.05. The histological analysis of TMJ tissue reveals key differences between healthy, osteoarthritic, and rhPRG4-treated joints. The intra-articular infiltration of rhPRG4 in TMJ-OA has a cartilage and articular disc repair effect, reducing the severity of osteoarthritis and promoting a more organized cartilage structure, with slightly better results at the 30 μg/mL concentration.

Background: Early-life stress and dietary habits are key determinants of metabolic health. This study investigates the combined effects of maternal separation (MS) and a post-weaning high-fat diet (HFD) on liver morphology in male C57BL/6 mice. Methods: Male mice were subjected to MS during early postnatal life or kept unmanipulated (UM). After weaning, animals were assigned to either a control diet (CD) or an HFD, forming four groups: UM-CD, UM-HFD, MS-CD, and MS-HFD. Liver histology, collagen deposition, and both morphometric and stereological parameters were assessed following 16 weeks of dietary intervention. Results: MS and HFD independently altered liver structure, while the combination of both factors intensified these changes. The MS-HFD group exhibited pronounced steatosis, mixed inflammatory infiltrates, and hepatocellular ballooning, with a significantly higher NAFLD Activity Score (NAS). No significant differences were observed in liver fibrosis. Morphometric analysis revealed increased body mass in HFD-fed groups and elevated liver mass in MS-HFD. Liver volume was higher in MS-HFD, though not significantly. Liver stereology revealed reduced numerical density of hepatocytes (Nv_hep) and increased surface density (Sv_hep) in MS groups, with the most pronounced effects in MS-HFD. Conclusions: Maternal separation amplifies the hepatic alterations induced by HFD, promoting early inflammatory and steatotic changes. These findings highlight the significance of early-life stress as a factor increasing susceptibility to diet-induced liver damage.