Volume 6 Issue 5, May 2024

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.

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.

Maternal circadian rhythms influence the health of infants. Cui, Xu and colleagues find that disruption of maternal rhythms impairs neonatal immune cell function and aggravates neonatal inflammatory disorders, which can be rescued by the administration of docosahexaenoic acid (a metabolite found in breast milk).

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.

Agmatine produced by gut microbiota — specifically, Bacteroides vulgatus — activates the farnesoid X receptor (FXR) in intestinal epithelial L cells in a bile-acid-independent manner, which inhibits host glucagon peptide 1 (GLP-1) secretion and leads to polycystic ovary syndrome (PCOS) in mice. Supplementing mice with the GLP-1 receptor (GLP-1R) agonist liraglutide or inhibiting the production of agmatine reverses the PCOS phenotype.

Nguyen and Corvera review distinct changes that occur in adipose tissue during ageing, discuss potential mechanisms by which these changes impact whole-body metabolism, immunity and longevity, and highlight therapeutic opportunities.

Sharma et al. review the regulation and biological functions of apparently ‘futile’ dynamic lipid cycle in regulating whole-body metabolic homeostasis.

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.

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.

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

Klingelhuber, Frendo-Cumbo et al. develop a proteomic atlas elucidating the intracellular spatiotemporal changes in protein levels and localizations during human adipogenesis.

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.

In mice, disruption of circadian rhythms during pregnancy aggravates neonatal inflammation via metabolic reprograming of myeloid cells in the offspring.

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

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

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.

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.