Effect of Fatty Acid–Binding Protein 4 Inhibition on Rotator Cuff Muscle Quality: Histological, Biomechanical, and Biomolecular Analysis

Abstract

Background: A rotator cuff tear (RCT) induces fatty acid–binding protein 4 (FABP4) expression, resulting in ectopic fat accumulation in the rotator cuff muscle. Purpose: To evaluate whether FABP4 inhibition reduces fatty infiltration and improves muscle physiology after RCT in a rat model. Study Design: Controlled laboratory study. Methods: Human supraspinatus muscle and deltoid muscle tissues were acquired from patients with RCTs during arthroscopic surgery, and FABP4 expression in the supraspinatus muscle was evaluated as compared with the intact deltoid muscle. A rat RCT model was established by detaching the supraspinatus tendon, after which a specific FABP4 inhibitor was locally injected into the supraspinatus muscle 4 times at 3-day intervals starting 2 weeks after the surgery. Body weight and blood glucose levels were measured at 2 and 4 weeks after the RCT, and the mRNA and protein expressions of various target molecules (including FABP4), histological changes, and biomechanical tensile strength were assessed in the supraspinatus muscles at 4 weeks after the RCT. Results: The expression of human FABP4 was significantly increased in the torn rotator cuff muscle as compared with the intact deltoid muscle. In the rat model, the mRNA and protein expressions of FABP4 and HIF1α were significantly increased by the RCT as compared with the control. The FABP4 inhibitor treatment significantly decreased FABP4 expression when compared with the vehicle treatment; however, HIF1α expression was not significantly decreased versus the vehicle treatment. Histologically, RCT induced noticeable muscle fatty infiltration, which was remarkably reduced by the local injection of the FABP4 inhibitor. Biomechanically, the tensile strength of the rotator cuff muscle after the RCT was significantly improved by the FABP4 inhibitor in terms of load to failure and total energy to failure. Conclusion: RCT induces FABP4 expression in human and rat rotator cuff muscles. The FABP4 inhibitor drastically decreased the histological fatty infiltration caused by RCT and improved the tensile strength of the rotator cuff muscle. Clinical Relevance: FABP4 inhibitor may have a beneficial effect on the muscle quality after RCT.