{Reference Type}: Journal Article {Title}: Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes. {Author}: Mori H;Peterson SK;Simmermon RC;Overmyer KA;Nishii A;Paulsson E;Li Z;Jen A;Uranga RM;Maung JN;Yacawych WT;Lewis KT;Schill RL;Hetrick T;Seino R;Inoki K;Coon JJ;MacDougald OA; {Journal}: Mol Metab {Volume}: 83 {Issue}: 0 {Year}: 2024 May 14 {Factor}: 8.568 {DOI}: 10.1016/j.molmet.2024.101916 {Abstract}: 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.