Is orbital adipose tissue obesity-privileged? The relationship between small adipocyte size and metabolically healthy state from the view of orbital fat.

Abstract

Purpose: White adipose tissue (WAT) expands by increasing adipocyte size (hypertrophy) and/or number (hyperplasia) to handle excess energy and plays a key homeostatic role in lipid metabolism. Hypertrophic adipocytes have many impaired biological functions. In contrast, hyperplastic adipocytes can reduce the negative metabolic effects of obesity. Thus, understanding the mechanisms of adaptive WAT expansion is essential for optimizing lipid storage and preventing the adverse metabolic consequences of obesity. Hedgehog (Hh) signaling has been shown to improve adipose health and can be a pharmacological target to ameliorate obesity-induced metabolic abnormalities. Clinically, we found that the size of adipocytes in orbital fat (OF) is less affected by obesity, and we hypothesized that OF possesses a relatively metabolically healthy profile.

Methods: To verify our hypothesis, we identified multiple hallmarks of healthy adipose tissue in OF using a combination of bioinformatics-based transcriptomics analyses and experimental methods.

Results: Our results revealed that compared with abdominal subcutaneous fat (SF), OF had a smaller cell size, more dynamic ability to remodel the adipose extracellular matrix (ECM), higher vascular supply, and less macrophage infiltration. OF also showed promising adipogenic and proliferative capabilities and a healthy adipocytokine secretion pattern. Moreover, the Hh signaling was activated in OF and may influence depot-specific adipose health.

Conclusion: These findings collectively support that OF is generally in a naturally metabolically healthy state with high expandability and obesity-free privilege, providing new therapeutic ideas for obesity-related metabolic dysfunctions.