Stress-coping phenotypes shape adipose tissue function and plasticity and modulate metabolic resilience.

Area of Science:

• Metabolic research
• Obesity research
• Stress and physiology

Background:

• Stress resilience confers metabolic protection, particularly in high-fat diet (HFD) models.
• Adipose tissue is central to obesity comorbidities.
• Understanding how stress resilience impacts adipose tissue is crucial.

Purpose of the Study:

• To define how stress resilience influences adipose tissue function.
• To investigate the molecular and transcriptomic changes in adipose tissue of stress-resilient (Dominant, Dom) versus stress-vulnerable (Submissive, Sub) mice under standard (STD) or HFD.
• To assess the effects of pioglitazone and paroxetine on adipose tissue function.

Main Methods:

• Comparative analysis of Dom and Sub mice under STD and HFD conditions.
• Metabolic, molecular, and transcriptomic analyses of epididymal and inguinal white adipose tissue (eWAT and iWAT).
• Isolation of stromal vascular fraction (SVF) cells to assess adipogenic potential; investigation of drug effects (pioglitazone, paroxetine).

Main Results:

• Sub mice on HFD developed glucose intolerance and impaired insulin signaling, unlike metabolically protected Dom mice.
• Sub WAT showed adipocyte hypertrophy, unfavorable leptin/adiponectin ratios, and suppressed BCAA catabolism.
• Sub mice exhibited reduced SVF cell proliferation and adipogenic potential, with transcriptomic evidence of downregulated adipogenesis.
• Dom adipocytes showed higher Glut4, Ucp1, and favorable adiponectin/leptin mRNA ratios.
• Pioglitazone improved adipogenesis and insulin sensitivity in Sub mice; paroxetine normalized behavior and improved adipogenesis towards a Dom-like profile.

Conclusions:

• Impaired stress coping is linked to defects in adipose progenitor function.
• These defects contribute to maladaptive white adipose tissue (WAT) expansion and increased susceptibility to metabolic disease.
• Targeting stress response and adipose progenitor function may offer therapeutic strategies for obesity-related metabolic dysfunction.