Neurofibromin regulates metabolic rate via neuronal mechanisms in Drosophila

• DOI: 10.1038/s41467-021-24505-x
• Publication Date: 2021-07-13T10:24:02Z
• Authors: Valentina Botero; Bethany A. Stanhope; Elizabeth B. Brown; Eliza C. Grenci; Tamara Boto; Scarlet J. Park; Lanikea B. King; Keith R. Murphy; Kenneth J. Colodner; James A. Walker; Alex C. Keene; William W. Ja; Seth M. Tomchik
• Keywords: Neurofibromin 1

Abstract Neurofibromatosis type 1 is a chronic multisystemic genetic disorder that results from loss of function in the neurofibromin protein. Neurofibromin may regulate metabolism, though underlying mechanisms remain largely unknown. Here we show regulates metabolic homeostasis Drosophila via discrete neuronal circuit. Loss increases rate Ras GAP-related domain-dependent mechanism, feeding homeostatically, and alters lipid stores turnover kinetics. The increase independent locomotor activity, maps to sparse subset neurons. Stimulating these neurons rate, linking their dynamic activity state metabolism over short time scales. Our indicate mechanisms, suggest cellular systemic alterations represent pathophysiological mechanism neurofibromatosis 1, provide platform for investigating role homeostasis.