2015 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Leptin promotes systemic lupus erythematosus
Presenter: Elaine Lourenco
Division: Rheumatolgoy
☐Faculty ☐Fellow ☐Resident ☒Post-doc Research Fellow ☐Graduate Student ☐Medical Student ☐Other
Principal Investigator/Mentor: Antonio LaCava
Co-Investigators: Aijing Liu
Thematic Poster Category: Infections, Injury and Repair, Inflammation, Host Defense, Immunology, Hemostasis and
Atherosclerosis
Abstract
Leptin is an adipocytokine that plays an important role in the modulation of immune responses and in
the development of inflammation. Circulating leptin levels are elevated in systemic lupus
erythematosus (SLE) patients, yet it is not clear whether this association reflects a direct influence of
leptin on the development of SLE. To investigate this possibility, we compared the development of SLE
between leptin-deficient (ob/ob) and leptin-sufficient (wild type, WT) mice treated with the lupusinducing agent pristane. Leptin deficiency protected ob/ob mice from developing autoantibodies, renal
disease, and reduced the frequency of immuoregulatory cells as compared to leptin-sufficient WT
mice. The role of leptin in the development of SLE was confirmed in the (NZB x NZW)F1 (NZB/W)
mouse model of spontaneous SLE. Elevated plasma leptin levels correlated with disease
manifestations, and leptin administration accelerated the development of autoantibodies and renal
disease. Conversely, leptin antagonism delayed disease progression and increased the survival of
severely nephritic NZB/W mice. Together, these results suggest a direct pro-pathogenic role of leptin
in SLE, and envision the possibility of leptin antagonism for SLE immunotherapy.