Metabolomics, at the heart: With heart failure a leading cause of death, a better understanding of metabolic function in the heart is a welcome advance. Murashige et al. measured more than 270 metabolites using liquid chromatography–mass spectrometry in human blood samples taken from an artery entering the heart and from a vein leaving it. Differences thus reflected the metabolic processes at work in the heart. Their results confirmed that hearts voraciously consume fatty acids. Hearts secreted, rather than consumed, amino acids, thus revealing active proteolysis. In patients with heart failure, ketone and lactate consumption increased, as did proteolysis. These findings could lead to strategies for fighting heart disease by altering metabolism. Science , this issue p. 364

Fueling lymph node metastases: Metastatic cells can migrate from a primary tumor to distant organs through two routes: They can enter the bloodstream directly, or they can enter a lymph node adjacent to the primary tumor. Little is known about the biological mechanisms that allow tumor cells to survive and grow within lymph nodes. Studying mouse models, Lee et al. found that tumor cells adapt to the lymph node microenvironment by shifting their metabolism toward fatty acid oxidation. This occurs through activation of a signaling pathway driven by the yes-associated protein (YAP) transcription factor. Importantly, inhibition of fatty acid oxidation or YAP signaling suppressed lymph node metastasis in the mice. Science , this issue p. 644

The hepatocyte clock and food availability control gene expression and metabolism in nonhepatocytic cells in the liver.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) remain without effective therapies. The mechanistic target of rapamycin complex 1 (mTORC1) pathway is a potential therapeutic target, but conflicting interpretations have been proposed for how mTORC1 controls lipid homeostasis. We show that selective inhibition of mTORC1 signaling in mice, through deletion of the RagC/D guanosine triphosphatase–activating protein folliculin (FLCN), promotes activation of transcription factor E3 (TFE3) in the liver without affecting other mTORC1 targets and protects against NAFLD and NASH. Disease protection is mediated by TFE3, which both induces lipid consumption and suppresses anabolic lipogenesis. TFE3 inhibits lipogenesis by suppressing proteolytic processing and activation of sterol regulatory element–binding protein-1c (SREBP-1c) and by interacting with SREBP-1c on chromatin. Our data reconcile previously conflicting studies and identify selective inhibition of mTORC1 as a potential approach to treat NASH and NAFLD.