Orbital Fat is an Observation Model to Provide Insights into Adipocyte Hypertrophy and Hyperplasia During White Adipose Tissue Expansion.

Introduction: Obesity is a global health problem characterized by excessive white adipose tissue (WAT) distribution. Adipocyte hypertrophy (increased cell size) and hyperplasia (differentiation into new adipocytes from pre-adipocytes) are two ways for WAT to expand. The precedence of hypertrophy over hyperplasia leads to an enlarged adipocyte size, which is associated with multiple metabolic dysfunctions. Compared with abdominal subcutaneous fat (SF), orbital fat (OF) has smaller adipocytes with less inflammatory infiltration, better vascularization, and higher adipogenic and proliferative capacities, reflecting a healthy metabolic state. Polyunsaturated fatty acids (PUFAs) can stabilize energy homeostasis via G protein-coupled receptor 120 (GPR120) to alleviate insulin resistance and inflammation.

Methods: We used lipidomics analysis to reveal a greater accumulation of two PUFAs-arachidonic acid (AA) and docosapentaenoic acid (DPA) in OF than in SF and then hypothesized that AA/DPA is one factor regulating WAT morphological and biological heterogeneity.

Results: Mechanistically, the existing literature evidence suggests that AA/DPA signals may stimulate the co-activation and interaction of GPR120 and peroxisome proliferator-activated receptor γ (PPARγ), at least partially contributing to adipose metabolic health.

Conclusion: As the differential metabolites between OF and SF, AA and DPA, along with the relevant GPR120/PPARγ pathways, offer new therapeutic approaches for morbid obesity.