Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes

• Main Authors: Hiroyuki Mori (Author), Sydney K. Peterson (Author), Rachel C. Simmermon (Author), Katherine A. Overmyer (Author), Akira Nishii (Author), Emma Paulsson (Author), Ziru Li (Author), Annie Jen (Author), Romina M. Uranga (Author), Jessica N. Maung (Author), Warren T. Yacawych (Author), Kenneth T. Lewis (Author), Rebecca L. Schill (Author), Taryn Hetrick (Author), Ryo Seino (Author), Ken Inoki (Author), Joshua J. Coon (Author), Ormond A. MacDougald (Author)
• Format: Book
• Published: Elsevier, 2024-05-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

2212-8778
10.1016/j.molmet.2024.101916