In eukaryotic cells, the mammalian target of rapamycin complex 1 (sometimes referred to as the mechanistic target of rapamycin complex 1; mTORC1) orchestrates cellular metabolism in response to environmental energy availability. As a result, at the organismal level, mTORC1 signalling regulates the intake, storage and use of energy by acting as a hub for the actions of nutrients and hormones, such as leptin and insulin, in different cell types. It is therefore unsurprising that deregulated mTORC1 signalling is associated with obesity. Strategies that increase energy expenditure offer therapeutic promise for the treatment of obesity. Here we review current evidence illustrating the critical role of mTORC1 signalling in the regulation of energy expenditure and adaptive thermogenesis through its various effects in neuronal circuits, adipose tissue and skeletal muscle. Understanding how mTORC1 signalling in one organ and cell type affects responses in other organs and cell types could be key to developing better, safer treatments targeting this pathway in obesity. © Springer Nature Limited 2024.; The protein complex mTORC1 is a key regulator of cellular metabolism in response to energy availability. This Review discusses the role of mTORC1 in regulating energy expenditure and the implications for the development and treatment of obesity. © Springer Nature Limited 2024..; Mammalian target of rapamycin complex 1 (mTORC1) plays different and complex roles in the regulation of energy expenditure. mTORC1 cell-specific actions affect other cells and organs by altering cellular metabolism and the use of energy substrates while modifying inter-organ communication. mTORC1 activation is required for central sympathetic nervous system (SNS) stimulation and SNS effects on white adipose tissue (WAT), brown adipose tissue (BAT) and skeletal muscle, which lead to WAT browning and increased energy expenditure. mTORC1 stimulates non-shivering thermogenesis in BAT and skeletal muscle. mTORC1 is a master regulator of skeletal muscle metabolism and it is crucial for skeletal muscle mass maintenance. © Springer Nature Limited 2024..< Réduire