Exometabolomics Reveals Metabolic Modulation Induced by Chia Oil Supplementation in Adipose Tissue Explants From Obese Mice

ABSTRACT Obesity impairs adipose tissue metabolism and dietary interventions capable of modulating these alterations remain insufficiently explored. To investigate depot‐specific metabolic adaptations in subcutaneous (SAT) and epididymal adipose tissue (EAT) in response to chia oil supplementation. Male C57BL/6J mice received a control diet (C group) or a high‐fat diet (H group) for 8 weeks, followed by 5 weeks of chia oil supplementation (1.5% w/w; 1.5 g/100 g diet; CC and HC groups). Exometabolomic profiling of SAT and EAT explants was performed using 1 H‐NMR, accompanied by targeted gene‐expression analyses. Chia oil supplementation reduced adipocyte hypertrophy and improved glucose tolerance in obese mice without altering body or adipose tissue mass. Obesity markedly decreased l ‐histidine secretion in SAT and this effect was not modified by chia oil supplementation. In obese SAT, chia oil reduced l ‐valine and l ‐proline secretion and increased l ‐threonine levels, while it increased lactate secretion in obese EAT. Obesity did not significantly affect acetate secretion, although chia oil supplementation resulted in a depot‐specific variation exclusively in the HC group. Correlation analysis revealed that chia oil modified metabolic interaction networks in both adipose depots. Chia oil supplementation induced depot‐specific metabolic adjustments in SAT and EAT, highlighting the plasticity of adipose tissue and the potential of dietary lipids to modulate adipose metabolic networks.