267-LB: Diabetes-induced Insulin Resistance and DPP-4 Activity Can Be Alleviated through the Reduction of M1 Polarization of Adipose Tissue

Abstract

Dysregulation of M1/M2 polarization in adipose tissues is emerging as a central mechanism underlying the pathogenesis of obesity and comorbidities such as insulin resistance and nonalcoholic fatty liver disease. To define the involvement of dysregulation of M1/M2 polarization of adipose tissues in diabetes and the effect of nondiabetic plasma on M1/M2 polarization of adipose tissue and liver as well as dipeptidyl peptidase-4 (DPP-4) activity in plasma, we purified stromal vascular fractions (SVFs) from diabetic and nondiabetic mice and analyzed their M1/M2 polarization with or without the treatment of nondiabetic plasma. SVF of diabetic mice (Lep-/-) demonstrated a significant increase of M1 but decrease of M2 signature as compared with nondiabetic mice (Lep+/-). Treatment of SVF from adipose tissue of Lep-/- mice with plasma of Lep-/- mice in vitro significantly increased M1 gene signature. Treatment of SVF from adipose tissue of Lep-/- mice with plasma of nondiabetic mice (Lep+/- mice) increased M2 gene signature. Moreover, injection of plasma of nondiabetic mice (Lep+/-) to adipose tissue of diabetic mice (Lep-/-) induces M2 expression of SVF and decreases inflammation of liver and DPP-4 activity of diabetic (Lep-/-) mice. These data suggest that plasma of diabetic mice can induce M1 expression and plasma of nondiabetic mice can induce M2 expression of adipose tissue of diabetic mice. In conclusion, diabetes and obesity-induced insulin resistance, glucose intolerance, and systemic inflammation can be alleviated through the reduction of M1 polarization of adipose tissue. Disclosure L. Chen: None. Funding Taiwan Ministry of Science and Technology (MOST 107-2314-B-010-043-MY3)