%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.