Research articles

The LITMUS consortium provides a resource of rodent MASLD models benchmarked against metabolic, histologic and transcriptomic features that are relevant for human MASLD. The work is useful for selecting relevant rodent models for studying this common disease.

Lim, Adler et al. show that the urea cycle enzyme ASS1 can function in the nucleus to supply fumarate necessary to drive DNA damage responses.

Sekine et al. show that macrophages utilize different pathways to sense acute and chronic hypoxia, the latter relying preferentially on PNPO–PLP rather than hypoxia-inducible factors.

The transcriptional coregulators YAP/TAZ are shown to directly control leptin gene transcription, thereby uncoupling adipose tissue mass from leptin levels.

Exercise during the early active phase leads to more robust bone growth and maturation in young mice, through a mechanism dependent on oxidative phosphorylation.

Jiménez-Blasco et al. show that neurons exhibit moderately low glycolytic rates despite their activity being mainly supported by glucose to preserve redox balance.

Tan et al. identify a regulatory network between colonic EECs and the gut microbiota that controls l-glutamic acid production, appetite and body weight in mice.

Upon nutrient stress in hepatocellular carcinoma, the glycolytic enzyme PFKL facilitates mitochondria tethering to lipid droplets to engage lipid mobilization and ensure nutrient supply.

The metabolite agmatine derived from the gut microbiota contributes to a polycystic ovary syndrome-like phenotype in female mice and inhibits the secretion of glucagon-like peptide-1, thereby contributing to metabolic and ovarian dysfunction.

Sung et al. provide a powerful pipeline based on deep mutational scanning to elucidate the molecular mechanisms of mitochondrial complex I assembly and predict pathogenicity of mutations in complex I assembly factors.

Wang et al. provide insight into how acetate promotes tumour growth by reprogramming lung cancer metabolism and promoting immune evasion.

TGR5 activation improves myocardial lipid accumulation and cardiac dysfunction in diabetic mice, offering promise for managing 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.

Truncated version of adenylyl cyclase 3 acts as a cold-induced rheostat during long-term brown adipose tissue activation.

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.

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.

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.

The authors develop a metabolic engineering strategy for improving polyketide production of industrial interest and discovering new natural products in bacteria.

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.