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Brown adipose tissue acquires increased thermogenic capacity with prolonged cold exposure through de novo recruitment of brown adipocytes. Studies by Shamsi et al. and Angueira et al. identify novel cellular origins of cold-induced brown adipocytes and further elucidate the molecular mechanism regulating the expansion of brown adipose tissue.
Redox cofactors are essential for the metabolic reactions that support cell proliferation. NADPH is important both to combat oxidative stress and to facilitate reductive reactions in biosynthesis. In this issue, Tran et al. find that the enzyme that produces mitochondrial NADPH is critical in enabling proline synthesis to support cell proliferation when environmental proline is limited.
Learning to balance work, family, optimism and setbacks is a process for all early-career investigators. Stephanie Correa and Leng Han share their stories in this instalment of Career pathways.
Obesity is associated with mitochondrial dysfunction and chronic metabolic derailment. Cho et al. report that elevated adipose expression of the Hippo kinases STK3 and STK4 (STK3/4) in obesity and type 2 diabetes decreases the mass and oxidative capacity of adipocyte mitochondria. Genetic or pharmacological inhibition of STK3/4 restores mitochondrial mass and function in adipocytes and improves glucose homeostasis in mice with diet-induced obesity. These findings support STK3/4 as new targets for obesity-related diseases.
It is self-evident that consuming alcohol affects brain function and behaviour. What is not clear, however, is how alcohol does so. A new study shows that impairments in balance and motor coordination evoked by low-dose alcohol are mediated not by ethanol itself but by one of its metabolites, which is produced locally by astrocytes in the brain rather than in the liver.
Nutrient availability dictates cell differentiation and transition through the Dictyostelium discoideum life cycle. Kelly et al. reveal that the increase in reactive oxygen species associated with nutrient limitation coincides with a sequestration of available cysteine in glutathione, thus limiting sulfur-dependent mitochondrial respiration and promoting aggregation into the differentiated spore form.
Quarta et al. discuss POMC neuronal heterogeneity and how specific subpopulations of POMC neurons can have diverse effects on appetite, whole-body metabolic physiology and the development of obesity.
Deciphering the origins of the various cells in atherosclerotic plaques, the regulation of their fates and their functions is an essential step towards developing strategies to limit or even reverse disease progression to myocardial infarction. In this issue, Newman et al. advance our understanding of the roles of non-vascular smooth muscle cells in the formation and maintenance of the fibrous cap, a structure in human atherosclerotic plaques that protects them against rupture—the proximal event typically underlying myocardial infarctions.
Exhaustion of pancreatic beta cells in the face of prolonged insulin resistance results in the development of type II diabetes. Ansarullah et al. now describe an inhibitor of beta-cell insulin signalling that, on removal, increases beta-cell mass and improves beta-cell function, with potential as a new way to address beta-cell failure.
Cancer cells undergo metabolic rewiring to support unrestrained proliferation, but dependence on oncogenesis-supportive metabolites could be leveraged therapeutically. Geeraerts et al. explore the centrality of serine and glycine metabolism to cancer survival, and how targeting the de novo serine and glycine synthesis pathways can complement current therapies.
Mitochondrial diseases are caused by genetic variants in either nuclear or mitochondrial DNA, and they have no known treatments. A new study by Perry et al. in this issue of Nature Metabolism used a drug screen to identify the widely available antibiotic doxycycline, an inhibitor of mitochondrial translation, as a potential pharmacological treatment for mitochondrial diseases.
A creatine futile cycle has been shown to contribute to energy expenditure in beige adipocytes in preclinical mouse models of obesity. In this issue of Nature Metabolism, Connell and colleagues show that creatine supplementation in healthy young female vegetarians unfortunately affects neither human brown adipocyte activity nor cold-induced energy expenditure.
Liver function depends on the temporal and zonal distribution of complementary metabolic tasks in hepatocytes. A new study by Droin et al. highlights how chronobiology and liver zonation orchestrate liver metabolism at single-cell resolution.
Gribble and Reimann provide a concise overview of the core physiology of GLP-1 secretion and action, and the roles of GLP-1 in human health, disease and therapy.
In this instalment of Career pathways, Jing Fan and Edward A. Phelps reflect on fostering their newly formed research programs in the face of challenges both familiar and new.
The tumour microenvironment (TME) is a unique cellular and metabolic landscape. Elia and Haigis describe how metabolism influences, and is affected by, the complexity of cellular interactions within the TME and highlight opportunities for therapeutic intervention.
Van Gastel and Carmeliet provide an overview of emerging findings on how cellular metabolism shapes skeletal stem cell fate and function, and discuss how metabolic dysregulation might contribute to skeletal ageing and degenerative diseases.
