For infectious-disease outbreaks, clinical solutions typically focus on efficient pathogen destruction. However, the COVID-19 pandemic provides a reminder that infectious diseases are complex, multisystem conditions, and a holistic understanding will be necessary to maximize survival. For COVID-19 and all other infectious diseases, metabolic processes are intimately connected to the mechanisms of disease

Maternal exercise during pregnancy results in metabolic benefits for offspring, but how mothers transfer these benefits to newborns has been a mystery. A new study now shows that a breast-milk component transmits the metabolic effects of exercise to offspring

Poor maternal environments, such as under- or overnutrition, can increase the risk for the development of obesity, type 2 diabetes and cardiovascular disease in offspring1,2,3,4,5,6,7,8,9. Recent studies in animal models have shown that maternal exercise before and during pregnancy abolishes the age-related development of impaired glucose metabolism10,11,12,13,14,15, decreased cardiovascular function16

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Per capita fructose consumption has increased 100-fold over the last century1. Epidemiological studies suggest that excessive fructose consumption, and especially consumption of sweet drinks, is associated with hyperlipidaemia, non-alcoholic fatty liver disease, obesity and diabetes2,3,4,5,6,7. Fructose metabolism begins with its phosphorylation by the enzyme ketohexokinase (KHK), which exists in two

The transition from senior postdoc to early-stage investigator is a pivotal step in the careers of academic scientists. In this series, early-stage investigators reflect on their labs’ first publications and the journeys that led them there.

The SARS-CoV-2 pandemic has posed one of the greatest scientific challenges to our society in a century. The accompanying disruption will have a disproportionally large effect on the careers of early-stage investigators and will require concrete action to preserve a generation of scientists.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

T cells undergo metabolic rewiring to meet their bioenergetic, biosynthetic and redox demands following antigen stimulation. To fulfil these needs, effector T cells must adapt to fluctuations in environmental nutrient levels at sites of infection and inflammation. Here, we show that effector T cells can utilize inosine, as an alternative substrate, to support cell growth and function in the absence

Catecholamines stimulate the mobilization of stored triglycerides in adipocytes to provide fatty acids (FAs) for other tissues. However, a large proportion is taken back up and either oxidized or re-esterified. What controls the disposition of these FAs in adipocytes remains unknown. Here, we report that catecholamines redirect FAs for oxidation through the phosphorylation of signal transducer and

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and death worldwide. Peroxynitrite, formed from nitric oxide, which is derived from inducible nitric oxide synthase, and superoxide, has been implicated in the development of emphysema, but the source of the superoxide was hitherto not characterized. Here, we identify the non-phagocytic NADPH oxidase organizer 1 (NOXO1) as the

Non-alcoholic steatohepatitis (NASH) is characterized by lipotoxicity, inflammation and fibrosis, ultimately leading to end-stage liver disease. The molecular mechanisms promoting NASH are poorly understood, and treatment options are limited. Here, we demonstrate that hepatic expression of bone morphogenetic protein 8B (BMP8B), a member of the transforming growth factor beta (TGFβ)–BMP superfamily

Little is known about regulated glucagon secretion by human islet α-cells compared to insulin secretion from β-cells, despite conclusive evidence of dysfunction in both cell types in diabetes mellitus. Distinct insulins in humans and mice permit in vivo studies of human β-cell regulation after human islet transplantation in immunocompromised mice, whereas identical glucagon sequences prevent analogous

We have lost a distinguished biochemist who dedicated his career to the study of phosphatidylinositol signalling in metabolic regulation and to the advancement of lipidomics.

Genetic-interaction mapping and co-essentiality analyses in human cells reveal the orphan gene C12orf49 (also known as SPRING1) as a novel regulator of lipid-metabolism homeostasis.

The de novo synthesis of fatty acids has emerged as a therapeutic target for various diseases, including cancer. Because cancer cells are intrinsically buffered to combat metabolic stress, it is important to understand how cells may adapt to the loss of de novo fatty acid biosynthesis. Here, we use pooled genome-wide CRISPR screens to systematically map genetic interactions (GIs) in human HAP1 cells

Coessentiality mapping has been useful to systematically cluster genes into biological pathways and identify gene functions1,2,3. Here, using the debiased sparse partial correlation (DSPC) method3, we construct a functional coessentiality map for cellular metabolic processes across human cancer cell lines. This analysis reveals 35 modules associated with known metabolic pathways and further assigns

Type 1 diabetes (T1D) is characterized by pancreatic beta cell dysfunction and insulin depletion. Over 40% of people with T1D manage their glucose through multiple injections of long-acting basal and short-acting bolus insulin, so-called multiple daily injections (MDI)1,2. Errors in dosing can lead to life-threatening hypoglycaemia events (<70 mg dl−1) and hyperglycaemia (>180 mg dl−1), increasing

Whereas textbooks depict metabolism in perfect homeostasis, disturbances occur in real life. One particularly relevant disturbance, caused by excess food and alcohol consumption and exacerbated by genetics, is reductive stress. New work by Goodman et al. identifies a biomarker of reductive stress and uses a gene therapy solution in mice. This work suggests how exercise and an accessible nutritional

Following activation, macrophages undergo extensive metabolic rewiring1,2. Production of itaconate through the inducible enzyme IRG1 is a key hallmark of this process3. Itaconate inhibits succinate dehydrogenase4,5, has electrophilic properties6 and is associated with a change in cytokine production4. Here, we compare the metabolic, electrophilic and immunologic profiles of macrophages treated with

Thermogenic adipocytes can burn lipids and carbohydrates for heat generation. The finding that a primate-specific long non-coding RNA regulates lipolysis and respiration in thermogenic adipocytes reveals a new mechanism controlling thermogenic adipocyte metabolism in humans.

Human thermogenic adipose tissue mitigates metabolic disease, raising much interest in understanding its development and function. Here, we show that human thermogenic adipocytes specifically express a primate-specific long non-coding RNA, LINC00473 which is highly correlated with UCP1 expression and decreased in obesity and type-2 diabetes. LINC00473 is detected in progenitor cells, and increases

Non-alcoholic fatty liver disease and steatohepatitis are highly associated with obesity and type 2 diabetes mellitus. Cotadutide, a glucagon-like protein-1 receptor (GLP-1R) and glucagon receptor (GCGR) agonist, was shown to reduce blood glycaemia, body weight and hepatic steatosis in people with type 2 diabetes mellitus. Here, we demonstrate that the effects of cotadutide in reducing body weight

Mitochondria are multidimensional organelles whose activities are essential to cellular vitality and organismal longevity, yet underlying regulatory mechanisms spanning these different levels of organization remain elusive1,2,3,4,5. Here we show that Caenorhabditis elegans nuclear transcription factor Y, beta subunit (NFYB-1), a subunit of the NF-Y transcriptional complex6,7,8, is a crucial regulator

As the metabolism community has grown and diversified with scientists from multidisciplinary backgrounds, metabolic terminology has evolved and expanded. In this Comment, we reflect on this new vernacular and how established terminology can guide future discussions of metabolic research.

Mammalian kidneys constantly filter large amounts of liquid, with almost complete retention of albumin and other macromolecules in the plasma. Breakdown of the three-layered renal filtration barrier results in loss of albumin into urine (albuminuria) across the wall of small renal capillaries, and is a leading cause of chronic kidney disease. However, exactly how the renal filter works and why its

Exposure to high glucose under inflammatory conditions is detrimental to insulin-secreting beta cells in the pancreas. Fu and colleagues describe a metabolic axis that decreases production of the ‘danger molecule’ nitric oxide and improves the survival of beta cells exposed to an inflammatory milieu, thus paving the way to new interventions for diabetes.

Chronic inflammation is linked to diverse disease processes, but the intrinsic mechanisms that determine cellular sensitivity to inflammation are incompletely understood. Here, we show the contribution of glucose metabolism to inflammation-induced changes in the survival of pancreatic islet β-cells. Using metabolomic, biochemical and functional analyses, we investigate the protective versus non-protective

The rhythmic regulation of transcriptional processes is intimately linked to lipid homeostasis, to anticipate daily changes in energy access. The Rev-erbα–HDAC3 complex was previously discovered to execute the rhythmic repression of lipid genes; however, the epigenetic switch that turns on these genes is less clear. Here, we show that genomic recruitment of MRG15, which is encoded by the mortality

An amendment to this paper has been published and can be accessed via a link at the top of the paper.