A one pathway model about the relationship between serum irisin and insulin resistance fits well (χ2 = 44.09, p < 0.001; CFI–0.994; TLI =0.986; and RMSEA = 0.067), and shows that elevated circulating irisin might improve insulin resistance indirectly through lowering fasting insulin levels (standardized path coefficient = −0.046, p = 0.032). The gene discussed is FNDC5; the disease is Insulin resistance.