The PDE4 inhibitor roflumilast reduces weight gain by increasing energy expenditure and leads to improved glucose metabolism

• DOI: 10.1111/dom.12839
• Publication Date: 2016-12-05T10:02:29Z
• Authors: Julia Möllmann; Florian Kahles; Corinna Lebherz; Ben Kappel; Christer Baeck; Frank Tacke; Christian Werner; Massimo Federici; Nikolaus Marx; Michael Lehrke
• Keywords: Roflumilast; Steatohepatitis

Aims To investigate the metabolic effects of phosphodiesterase‐4 (PDE4) inhibitor roflumilast, a clinically approved anti‐inflammatory drug used for treatment chronic obstructive pulmonary disease. Materials and methods The roflumilast were investigated in C57BL/6J mice, fed high‐fat Western‐type diet treated with or without period 12 weeks. Results Roflumilast led to marked reduction body weight gain, which became apparent second week after initiation was attributable pronounced increase energy expenditure. Furthermore, improved glucose tolerance, reduced insulin resistance diminished steatohepatitis mice. Mechanistically, this associated hepatic protein kinase A (PKA) cAMP response element binding (CREB) activation, leading peroxisome proliferator‐activated receptor gamma coactivator‐1α (PCG‐1α)‐dependent induction mitochondrial biogenesis. Consistently, increased cellular respiratory capacity hepatocytes PKA‐dependent manner. Conclusion Roflumilast‐dependent PDE4 inhibition is new target loss strategies, especially conditions comorbidities such as non‐alcoholic steatohepatitis.