Evaluation of Visceral Adipose Tissue Oxygenation by Blood Oxygen Level‐Dependent MRI in Zucker Diabetic Fatty Rats

Objective This study aimed to investigate the feasibility of blood oxygen level‐dependent magnetic resonance imaging (BOLD‐MRI) to evaluate visceral adipose tissue (VAT) oxygenation in Zucker diabetic fatty (ZDF) rats and its associations with systemic metaflammation. Methods Five‐week‐old ZDF rats and Zucker lean (ZL) rats were fed a high‐fat diet (HFD) for 18 weeks. A baseline BOLD‐MRI scan of perirenal adipose tissue was performed after 8 weeks of HFD feeding, and then the rats were randomized to receive pioglitazone or a vehicle for the following 10 weeks. At sacrifice, BOLD‐MRI scan, Hypoxyprobe‐1 injection, and circulating T helper 17 (Th17), regulatory T (Treg) cells, and monocyte subtype flow cytometry analysis were performed. Results HFD feeding led to a significant increase in VAT BOLD‐MRI R2* signals (20.14 ± 0.23 per second vs. 21.53 ± 0.20 per second; P = 0.012), an indicator for decreased oxygenation. R2* signal was significantly correlated with VAT pimonidazole adduct‐positive area, insulin resistance, Th17 and Treg cells, CD43 + and CD43+ + monocyte subtypes, and VAT macrophage infiltration. Pioglitazone treatment improved the insulin resistance and was associated with a delayed progression of VAT oxygenation. Conclusions This work demonstrated the feasibility of BOLD‐MRI for detecting the VAT oxygenation status in ZDF rats, and the BOLD‐MRI signals were associated with insulin resistance and systemic metaflammation in ZDF rats during the development of obesity.