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Significance Adipose tissue-derived mesenchymal stem cells (ADSCs) are well-known in the generation of both white and beige adipocytes and the maintenance of adipose tissue homeostasis. Stearoyl-coenzyme A desaturase 1 (Scd1) is a rate-limiting enzyme for monounsaturated fatty acids. Here, we show that deficiency of Scd1 promotes the formation of beige adipocytes in white adipose tissue by directing de novo beige adipogenesis. In the absence of Scd1, succinate accumulation was enhanced in ADSCs and fueled mitochondrial complex II activities. Notably, we demonstrate that succinate controls the potential of beige adipogenesis of ADSCs both in vitro and in vivo. These findings reveal an unidentified negative regulatory relationship between Scd1 and succinate during adipogenesis, holding great potential for combating obesity.

Scd1 controls de novo beige fat biogenesis through succinate-dependent regulation of mitochondrial complex II