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Mol Metab ; 83: 101916, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38492843

RESUMO

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. METHOD: 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. CONCLUSION: 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.


Assuntos
Adipócitos , Autofagia , Ácidos Graxos Monoinsaturados , Camundongos Knockout , Estearoil-CoA Dessaturase , Estearoil-CoA Dessaturase/metabolismo , Estearoil-CoA Dessaturase/genética , Animais , Camundongos , Adipócitos/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Ácidos Graxos Monoinsaturados/farmacologia , Camundongos Endogâmicos C57BL , Lisossomos/metabolismo , Sobrevivência Celular , Células 3T3-L1 , Masculino , Metabolismo dos Lipídeos , Autofagossomos/metabolismo
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