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Work in non-mammalian model organisms has shed light on many fundamental biological processes. At Nature Metabolism, we are interested in studies that make use of the unique advantages of these models to unravel new insights into metabolic biology.

Bondareva and Rodríguez-Aguilera et al. use scRNA-seq to analyze transcriptomes of 375,000 endothelial cells from seven organs in male mice at various stages of obesity to identify organ-specific vulnerabilities.

Shi et al. show that neuregulin-4 derived from brown adipose tissue can reduce endothelial injury and inflammation and alleviate atherosclerosis in male mice, via Akt and nuclear factor-κB signaling

The authors of this Perspective discuss the remarkable plasticity of the intestine in response to dietary and physiological changes, and highlight the importance of intestinal remodelling and metabolism in maintaining energy balance of the organism.

The immune-modulatory metabolite itaconate is secreted by myeloid-derived suppressor cells and taken up by CD8⁺ T cells to suppress their proliferation and function. In mice, blocking itaconate production enhances the efficacy of immune checkpoint blockade.

Itaconate is a metabolite with immune-modulatory effects in myeloid cells. In this study, Zhao, Teng et al. report an additional role for itaconate in CD8⁺ T cells, with implications for immune surveillance and anti-tumour immunity.

Prior to consuming a meal, food-odor perception is sufficient to trigger systemic lipid utilization in male mice.

As emerging clinical analyses suggest an increased risk of new-onset diabetes following COVID-19, a causal link and underlying mechanisms are yet to be established. Persistence of hyperglycaemia after disease regression and the potential infection of non-pancreatic tissue are adding another layer of complexity to the relationship between COVID-19 and diabetes mellitus.

Diener and Dai et al. analyse blood metabolites from 1,569 individuals and identify metabolites associated with the microbiome, host genetics or under hybrid genetic–microbiome control.

Malita, Kubrak et al. identify a circuit that drives food-specific appetites in Drosophila orchestrated by gut-derived Neuropeptide F.

Rahbani et al. show that the α₁-adrenergic receptor potentiates thermogenesis in thermogenic adipocytes, acting via Gα_q signalling, creatine kinase B and tissue-non-specific alkaline phosphatase.

Fenofibrate has been shown to inhibit SARS-CoV-2 replication in vitro. Results from a randomized clinical trial show that treating patients with COVID-19 with fenofibrate has no significant effect on clinically relevant outcomes.

Malita, Kubrak et al. show that the gut-derived hormone neuropeptide F suppresses sugar intake and increases the consumption of protein-rich food in Drosophila. This gives insight into the regulation of nutrient-specific appetite that ensures appropriate food choices to meet nutritional demands.

The human gut microbiome metabolizes hundreds of drugs, but the clinical relevance of these biotransformations remains unclear. Chen and colleagues show that gut bacterial nicotine metabolism protects against liver disease.

Scherer and colleagues demonstrate that manipulation of iron concentrations in the mitochondrial matrix of macrophages has profound effects on their polarization, leading to concomitant changes in adipocyte iron concentrations and, ultimately, systemic metabolic effects.

Using inducible transgenic mouse models, Joffin, Gliniak and colleagues demonstrate that altering mitochondrial iron levels in adipose tissue macrophages has profound effects on systemic metabolism in male mice.

The core metabolic pathways are tightly intertwined, creating challenges for metabolic engineering. Yu et al. present a synthetic decarboxylation cycle that substitutes the TCA cycle in energy metabolism, gaining high yields in the production of reduced compounds such as fatty acids.

In our tenth instalment of Career pathways, Jin Zhang and Christiane Wrann reflect on their journeys to becoming PIs and the importance of having a vision for your research, finding the right team, and sharing the joy of science through the training of students.

In this study, Yu et al. engineer a decarboxylation cycle in the yeast cytoplasm that provides increased reductive power to enhance bioproduction of reduced chemicals.