Reversal of the Obesity-Induced Exacerbation of Psoriasis by an Adiponectin Mimetic

Psoriasis is a common inflammatory skin disease affecting 125 million people. Obese individuals have a higher risk of psoriasis, greater severity of psoriatic lesions, and reduced response to biologic medications. However, we do not understand why and have no treatments to improve their responses. Our study builds on the discovery that adiponectin, produced by our fat cells, has anti-inflammatory properties. Obese patients, including with psoriasis, have less adiponectin in their skin compared to non-obese patients, and mouse models that cannot produce adiponectin have more severe psoriasis. A newly discovered molecule, ADP355, mimics adiponectin, but is more potent and has no known toxicity. Together with the Paller laboratory, I hypothesize that adiponectin deficiency plays a central role in the worsening of psoriasis with obesity. I will test in obese mouse models resembling psoriasis whether I can reverse the observed worsening associated with obesity by injecting ADP355. I will look for improvement in clinical response, the appearance of psoriasis under the microscope, and genetic changes in biomarkers typical of psoriasis. The proposed project may not only suggest a new adjunctive approach for treating psoriasis, but also promises to shed light on the role of adiponectin in inflammatory skin disease.