Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease

Baumeier, Christian; Schlüter, Luisa; Saussenthaler, Sophie; Laeger, Thomas; Rödiger, Maria; Alaze, Stella Amelie; Fritsche, Louise; Häring, Hans-Ulrich; Stefan, Norbert; Fritsche, Andreas; Schwenk, Robert Wolfgang; Schürmann, Annette

3.3. Elevated hepatic DPP4 activity leads to increased fat mass and adipose tissue inflammation Phenotypic characterization of HFD fed Dpp4-Liv-Tg mice revealed an increased body weight gain, which was due to an elevated fat mass rather than changes in lean mass (Figure 3AeC ). At 30 weeks of age, mass of white but not of brown adipose tissue was significantly increased in Dpp4-Liv-Tg mice ( Figure 3D ). Plasma triglyceride and free fatty acid concentrations did not differ, but cholesterol levels were elevated in mice with liver-specific Dpp4 overexpression (Table 1) . Since obesity is associated with adipose tissue inflammation, we next analyzed the expression of inflammatory markers in gonadal white adipose tissue. Indeed, the expression of the macrophage marker F4/ 80 (Emr1) and of proinflammatory cytokines (TNFa (Tnf) and MCP1 (Ccl2)) were increased in white adipose tissue of Dpp4-Liv-Tg mice ( Figure 3E ). In agreement, immunohistochemical staining of F4/80 showed higher abundance of macrophages in adipose tissue of Dpp4-Liv-Tg animals ( Figure 3F ).