Volume 1 Issue 9, September 2019

In this issue, Diehl et al. report that exogenous serine is essential for the cellular redox state and cancer nucleotide production, despite the ability of cancer cells to synthesize serine de novo in vitro.

Obesity is the result of an imbalance between caloric intake from the diet and energy expenditure. A new study provides evidence that alterations in calcium transport efficiency in muscle lead to an increased metabolic rate and protect mice against diet-induced obesity.

Dopamine is an important neurotransmitter with essential roles in movement control and salience, and implications in addiction as well as weight loss, decreased food intake and a reduced motivational drive to eat. Folgueira et al. now demonstrate that dopamine causes weight loss and increases brown adipose tissue temperature via activation of the dopamine receptor D2R in hypothalamic GABA-expressing neurons in mice, and treatment with the dopamine agonist cabergoline causes weight loss in humans.

A recent study by Esteghamat et al., published in Nature Genetics, has reported that CELA2A, encoding a pancreatic enzyme, is a novel genetic cause of metabolic syndrome and atherosclerosis.

Cells contributing to atherosclerotic disease are highly plastic and can shift their phenotype in a changing microenvironment. A study in Nature Metabolism now reveals that transforming growth factor-β (TGF-β) can transform endothelial cells into pro-inflammatory cells and that inhibition of TGF-β-receptor signalling in the endothelium can reverse atherosclerosis in mice.

Mammalian cell culture represents a cornerstone of modern biomedical research. There is growing appreciation that the media conditions in which cells are cultured can profoundly influence the observed biology and reproducibility. Here, we consider a key but often ignored variable, oxygen, and review why being mindful of this environmental parameter is so important in the design and interpretation of cell culture studies.

Cancer cells increase serine synthesis; however, exogenous serine is required for maximal proliferation. Here the authors show that the demand for oxidized NAD⁺ constrains serine synthesis, which is needed for purine production to support cell proliferation.

Asano et al. dissect the functional difference between the soluble and membrane-bound forms of RANKL. Membrane-bound RANKL is sufficient for most physiological RANKL functions, whereas soluble RANKL promotes bone metastases by stimulating tumour cell migration to bone, without affecting tumour cell growth or osteoclast differentiation.

The role of skeletal muscle in non-shivering thermogenesis is not fully elucidated. Here the authors show that, in muscle, phospholipids can influence whole-body metabolic rate and counteract obesity by altering calcium signalling and inducing energy expenditure.

Tajima and colleagues identify mitochondrial lipoylation as a post-transcriptional molecular signature of aged brown adipose tissue (BAT) in mice. Reduced mitochondrial lipoylation is tightly coupled with the age-associated decline in BAT function, whereas enhanced lipoylation restores BAT activity in aged mice.

The liver is a heterogeneous organ organized in lobules that are radially polarized. The use of single-cell spatial transcriptomics has revealed that half of hepatic genes are differentially expressed across the lobule. Ben-Moshe et al. show how a multi-omics approach, which consists of transcriptomics, micro RNA profiling and proteomics, allows for characterization of liver heterogeneity with higher resolution.

Chen et al. report that TGF-β signalling, although largely considered anti-inflammatory, has proinflammatory effects on endothelial cells. Inhibition of endothelial TGF-β signalling decreases atherosclerosis in mice and reverts established plaques, in part by decreasing endothelial-to-mesenchymal transitions.