Homeostasis articles from across Nature Portfolio

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.

The naked mole-rat exhibits extreme longevity, resistance to hypoxia and absence of cardiovascular disease. Here, Faulkes et al. identify mechanisms behind these traits by comparing cardiac metabolomes and transcriptomes of naked more-rats to other African mole-rat genera and evolutionary divergent mammals.

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.

Although obesity is associated with higher risk of cardiometabolic disease, high-protein diets can reduce fatness but still promote cardiometabolic disease. Zhang et al. address this contradiction and show that high-protein diets, and subsequently higher blood leucine levels, promote mTORC1 activation in macrophages in humans and mice, and that an increase in dietary leucine raises the risk of atherosclerosis in a mouse model.

In nature, organisms constantly face a variety of stresses in the environment. An organism’s ability to resolve a stressful state is crucial in maintaining homeostasis. In this issue of Nature Metabolism, Wei et al. report that redox-dependent caspase cleavage of fatty acid synthase triggers a global cue for stress resolution in Caenorhabditis elegans.

Neuronal energization and memory formation in the fruit fly are found to be conditioned by the shuttling of alanine between glial cells and neurons. This observation highlights the emerging role of energy metabolism as a driver of tissue function.

Group 3 innate lymphoid cells (ILC3s) maintain intestinal barrier integrity and nutrient absorption via IL-22; however, little is known about how these immune cells fuel effector function. Wu et al. now report that uptake of dietary proline acts as a critical metabolic modulator of the ILC3 transcriptome and cytokine production to maintain gut health.

A recent study reports that adenosine A2A receptor-mediated lymphangiogenesis increases lymphatic clearance of excess Na⁺ from the skin and reduces blood pressure, whereas impairment of this process leads to salt-sensitive hypertension. These findings raise intriguing physiological questions regarding the relationships among sodium, water and blood pressure.