The discovery of the archetypal adipocytokine leptin and how it regulates energy homeostasis have represented breakthroughs in our understanding of the endocrine function of the adipose tissue and the biological determinants of human obesity. Investigations on leptin have also been instrumental in identifying physio-pathological connections between metabolic regulation and multiple immunological functions. For example, the description of the promoting activities of leptin on inflammation and cell proliferation have recognized the detrimental effects of leptin in connecting dysmetabolic conditions with cancer and with onset and/or progression of autoimmune disease. Here we review the multiple biological functions and complex framework of operations of leptin, discussing why and how the pleiotropic activities of this adipocytokine still pose major hurdles in the development of effective leptin-based therapeutic opportunities for different clinical conditions.
The pleiotropic roles of leptin in metabolism, immunity, and cancer
Disclosures: C. Alviggi reported personal fees from Merck outside the submitted work. G. Matarese reported grants from Merck, personal fees from Merck, grants from Biogen, personal fees from Biogen, personal fees from Roche, personal fees from Novartis, and grants from IBSA outside the submitted work. No other disclosures were reported.
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Paola de Candia, Francesco Prattichizzo, Silvia Garavelli, Carlo Alviggi, Antonio La Cava, Giuseppe Matarese; The pleiotropic roles of leptin in metabolism, immunity, and cancer. J Exp Med 3 May 2021; 218 (5): e20191593. doi: https://doi.org/10.1084/jem.20191593
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