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Diabetes can cause heart failure by a toxic accumulation of lipids in cardiac myocytes, which impairs their function. This work shows that stimulation of the bile acid receptor TGR5 limits fatty acid uptake into cardiac myocytes and prevents the development of diabetic cardiomyopathy.
Using a multi-omics approach, the authors examine the molecular drivers of sexual dimorphism in the subcutaneous adipose tissue from sedentary and endurance-trained rats. These data provide a valuable resource for adipose tissue-related research.
Inhibitor of mitochondrial transcription treatment leads to reduced oxidative phosphorylation capacity but increases fatty acid oxidation in the liver, leading to protection from obesity and related pathology.
Sun et al. identify fatty acid binding protein 5 (FABP5) as a driver of obesity-induced hepatocellular carcinoma in mice. FABP5 inhibition is found to predispose transformed cells to death by ferroptosis and to induce a pro-inflammatory tumour microenvironment.
Optimization of energy and carbon–nitrogen allocation maximizes the proliferation and functionality of chimeric antigen receptor (CAR)-T cells. Lakhani et al. report that tonic signalling elements (scFvs) affect CAR-T cell metabolic fitness in an antigen-independent manner. A modest carbon–nitrogen emission (overflow) and resilient metabolic phenotype (compatibility) are associated with effective CAR-T cell therapy.
Lakhani et al. offer insight into the metabolic reconfigurations driven in T cells by chimeric antigen receptors (CARs) that differ only in their extracellular domains.
In this issue of Nature Metabolism, the research team of Mitchell Lazar reveals unexpected consequences of double loss of the coregulators NCOR1 and NCOR2 (NCOR1/2) in hepatocytes of adult mice, which affects chromatin functioning and glucocorticoid receptor (GR)-mediated gene transcription.
Hauck et al. show that during fasting, nuclear receptor corepressors 1 and 2 act together to activate the transcription of target genes, which is critical for the physiological response to fasting in mice.
A new engineering strategy for improving the biosynthesis of secondary metabolites in Streptomyces has been developed through the analysis of genes co-evolved with biosynthetic gene clusters. This strategy has been verified in 11 Streptomyces strains to enhance production of 16,385 metabolites, showing potential applications in drug discovery and industrial production.
The authors develop a metabolic engineering strategy for improving polyketide production of industrial interest and discovering new natural products in bacteria.
Thiazolidinediones (TZDs) are potent insulin-sensitizing drugs, but their use is accompanied by adverse side-effects. Rohm et al. now report that TZD-stimulated macrophages release miR-690-containing vesicles that improve insulin sensitization and bypass unwanted side-effects.
Recent technological advances permit the profiling of metabolic changes in single cells, which sheds light on how metabolism regulates immune responses. We advocate for accessible and standardized tools to reduce the barrier of entry to immunometabolism studies and facilitate the translation of fundamental findings towards clinical applications.
Rohm et al. show that small extracellular vesicles from adipose tissue macrophages from obese rosiglitazone-treated mice ameliorate glucose tolerance and insulin sensitivity in obese mice, while circumventing the adverse effects of rosiglitazone.
Kim et al. discover a subset of neurons that innervate the Drosophila intestine and act as postprandial taste-independent sensors for sodium, directing a behavioural preference for sodium following salt deprivation.