Dan Tachibana, Kazuo Nakamoto, Shogo Tokuyama*
Objective: Obesity is associated with the exacerbation of pain. Recently, it was reported that High-Fat Diet (HFD)-induced obese mice show mechanical hypersensitivity after surgery, which causes neuroinflammation via microglial activation in the hypothalamus. However, the mechanism by which HFD-induced obesity exacerbates pain remains unclear. The Fatty Acid-Binding Protein (FABP) 3 belongs to a family of proteins that transports fatty acids into the cell and modulates cellular functions. We demonstrated that FABP3 was increased in the hypothalamus of postoperative pain mice, and was co-expressed in microglia. FABP3 has a high affinity for saturated Fatty Acids (FAs) and n-6 polyunsaturated FAs in HFD-fed mice, and its function is affected by different types of FAs. Here, we tested whether FABP3 is involved in the mechanism of obesityinduced pain exacerbation through microglial regulation. Methods: C57/BL6J wild-type (WT) and FABP3 knockout (FABP3KO) mice were used in this study. These mice were fed a Control Diet (CD) or a High-Fat Diet (HFD) for eight weeks. Post-operative pain model mice were created by paw incision. Mechanical hypersensitivity was assessed using the von Frey test. Microglial expression and perimeters were analyzed using Iba-1. Results: Wild-Type (WT) mice fed a HFD (WT/HFD) showed continuous mechanical hypersensitivity for seven days after surgery compared to WT mice fed a CD. FABP3KO mice fed a HFD (FABP3/HFD) showed a significantly reduced response time to mechanical stimuli compared to WT/HFD and recovered mechanical hypersensitivity seven days after surgery. WT/HFD mice showed increased microglial expression and morphological hypertrophy of cells with an increase in their perimeter in the median eminence of the hypothalamus seven days after surgery, whereas these changes were not observed in FABP3/HFD mice. Conclusion: Our results showed that the deficiency of FABP3 may suppress HFD-induced pain exacerbation by regulating the hypothalamic microglia, indicating that FABP3 may be a therapeutic target for obesity-induced pain exacerbation.
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