Stress-Coping Phenotypes Shape Adipose Tissue Function and Plasticity and Modulate Metabolic Resilience

This study investigated how stress-coping phenotypes (stress-resilient Dominant and stress-vulnerable Submissive mice) shape white adipose tissue (WAT) function under standard and high-fat diet (HFD) conditions. Metabolic, molecular, and transcriptomic analyses were performed on epididymal (eWAT) and inguinal (iWAT) white adipose tissue. Results revealed that stress-vulnerable mice exhibit impaired adipogenesis, adipocyte hypertrophy, unfavorable adipokine profiles, and defective insulin signaling in WAT under HFD. Transcriptomic profiling by RNA-seq identified adipogenesis, fatty acid metabolism, and oxidative phosphorylation as differentially regulated pathways between the strains. Functional analyses confirmed reduced proliferative and adipogenic potential of stromal vascular fraction (SVF) cells from stress-vulnerable mice. Pharmacological activation of PPARgamma (pioglitazone) improved adipogenesis and metabolic parameters, while antidepressant treatment (paroxetine) normalized behavioral deficits and improved adipogenic capacity in stress-vulnerable mice.