%0 Journal Article %T Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes. %A Mori H %A Peterson SK %A Simmermon RC %A Overmyer KA %A Nishii A %A Paulsson E %A Li Z %A Jen A %A Uranga RM %A Maung JN %A Yacawych WT %A Lewis KT %A Schill RL %A Hetrick T %A Seino R %A Inoki K %A Coon JJ %A MacDougald OA %J Mol Metab %V 83 %N 0 %D 2024 May 14 %M 38492843 %F 8.568 %R 10.1016/j.molmet.2024.101916 %X OBJECTIVE: Exposure of adipocytes to 'cool' temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (Scd1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. The goal of this study is to further investigate the roles of Scd in adipocytes.
METHODS: In this study, we employed Scd1 knockout cells and mouse models, along with pharmacological Scd1 inhibition to dissect the enzyme's function in adipocyte physiology.
RESULTS: Our study reveals that production of monounsaturated lipids by Scd1 is necessary for fusion of autophagosomes to lysosomes and that with a Scd1-deficiency, autophagosomes accumulate. In addition, Scd1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of Scd1-deficient adipocytes.
CONCLUSIONS: This study demonstrates the indispensable role of Scd1 in adipocyte survival, with its inhibition in vivo triggering autophagy-dependent cell death and its depletion in vivo leading to the loss of bone marrow adipocytes.