Search

The authors provide a comprehensive characterization of how glutamine uptake and utilization regulate macrophage function in atherosclerosis.

Murcy et al. show that increasing the plasma glutamine-to-glutamate ratio in atherosclerosis can distally reprogram transcriptional and post-transcriptional remodeling of the aorta by GLS2-dependent hepatic glutaminolysis.

In this Review, Yvan-Charvet and colleagues discuss how cardiovascular risk factors and metabolic modifiers of atherosclerosis influence metabolism-dependent haematopoietic stem cell skewing (haematometabolism) and efferocyte reprogramming (efferotabolism) and highlight potential therapeutic strategies to reduce the risk of atherosclerosis by rebalancing haematopoiesis and efferocytosis.

Glycolysis provides building blocks for the proinflammatory activation of macrophages and simultaneously generates pyruvate. In this issue of Nature Metabolism, Ran et al. provide evidence that the transport of pyruvate to fuel the Krebs cycle in the mitochondria is not required in the inflammatory response.

Dietary fibers have beneficial effects on both metabolism and immunity. Here the authors demonstrate that type 2 dendritic cells mediate fibers benefits on Th17 cells homeostasis and glucose metabolism in the context of high-fat diet feeding.

Monocytes participate in plaque formation, and adapt to metabolic changes to alter their functions. Here the authors show, using genetic mouse models and functional analyses, that Glut1-mediated glucose metabolism is important for regulating monocyte homeostasis and migration, but curiously has no impact on atherosclerotic plaque formation.

To mature, dendritic cells collect and synthesize cholesterol to construct lipid nanodomains on their membranes. Obstructing this process impairs their ability to prime T cells.

Adipose tissue is composed of a number of adipocytes and a number of other cells including immune cells. Here the authors use single-cell sequencing of murine brown adipose tissue immune cells and describe multiple macrophage and monocyte subsets and show that monocytes contribute to brown adipose tissue expansion.

Merlin et al. find that non-canonical glutamine transamination is required for macrophage efferocytosis in atherosclerotic plaques by sustaining redox buffering and fueling energy production for cytoskeletal rearrangements.

Cholesterol efflux is mediated by specific transporters in T cells. Here the authors show that when the ABCA1/ABCG1 cholesterol transporters are absent, peripheral T cell numbers are reduced but activation increased with a premature aging phenotype of T cell senescence and apoptosis in middle aged Ldlr^−/− mice.

In this Review, the authors describe the bidirectional crosstalk between lysosome biology and immune cell function and polarization, focusing on immunometabolic reprogramming in the context of atherosclerosis and highlighting knowledge gaps and potential therapeutic strategies targeting immune cell lysosomes.

Here, the authors present the upstream pathway that controls the activation of the NLRP3 inflammasome during bacteraemia. The CNF1 toxin from Escherichia coli activates the Rho GTPase Rac2 and its activity is sensed by NLRP3, which is activated by a signalling cascade involving p21-activated kinases 1 and 2.

Nan Wang and colleagues uncover a new function for HDL that may contribute to its anti-atherosclerotic effects. In the bone marrow, HDL removes cholesterol from megakaryocyte progenitor cells in a process requiring the cholesterol transporter ABCG4, thereby dampening megakaryocyte and platelet production.

The accumulation of cholesterol in macrophages and other immune cells promotes inflammatory responses. Inflammation, in turn, reduces the normal physiological excretion of cholesterol, which amplifies the inflammatory response and promotes myelopoiesis. Here, the authors detail the mechanisms by which cholesterol accumulation affects immune signalling pathways and highlight potential therapeutic interventions that may have benefits for metabolic diseases.