Reviews & Analysis

Enerbäck and Rabinowitz summarize emerging evidence that lactate serves as a universal circulating fuel for mammalian cells.

Caffa et al. report in Nature that hormone-receptor-positive breast cancer is sensitive to a form of ‘dietary augmentation therapy’ that implements periods of fasting, thus enhancing anti-cancer therapy.

In this issue of Nature Metabolism, Mi and colleagues provide evidence that super-enhancers play a critical role in autosomal-dominant polycystic kidney disease (ADPKD) and show that CDK7 targeting provides a novel therapeutic option.

A study published in this issue of Nature Metabolism adds to the emerging evidence that the small intestine is an initial site of dietary fructose metabolism, especially at low fructose doses, thus decreasing exposure of the liver and the colonic microbiome to intact fructose.

Pancreatic adenocarcinoma (PDAC) is often characterized by substantial amounts of fibrosis, and how these stromal components affect metabolite availability is not fully understood. Zhu et al. now show that cancer-associated fibroblasts consume branched-chain amino acids (BCAAs) at high levels but release corresponding branched-chain α-ketoacids that support PDAC cell growth.

The adipose tissue harbours multiple immune-cell types whose populations are known to be altered in disease conditions. A new study by Brigger et al. shows that restocking fat tissues of old mice with eosinophils prevents age-related declines in physical and immunological functions.

Selenium is a micronutrient essential for the generation of selenoproteins, which function predominantly by detoxifying cellular reactive oxygen species. In this issue, Carlisle et al. describe a novel mechanism whereby perturbing selenium utilization via inhibition of SEPHS2, a component of the selenocysteine-biosynthesis pathway, results in selenide poisoning and cancer cell death.

The importance of metabolism in the course of SARS-Cov-2 infection is highlighted by the metabolic comorbidities of COVID-19. In this Perspective, Ayres provides insight into how current knowledge of immunometabolism and metabolic diseases can inform the understanding of COVID-19 pathology, and proposes potential metabolism-based clinical solutions.

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

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.

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.

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 technology can synergistically increase catabolism and relieve reductive stress.

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.

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.

Maintaining cellular NAD levels through supplementation with intermediates of NAD synthesis has considerable health benefits. A new study demonstrates that the reduced form of nicotinamide riboside, NRH, can be converted to NAD in a biosynthetic pathway that involves adenosine kinase, thus strongly boosting NAD levels in cells and tissues.

He et al. highlight the potential, and some of the drawbacks, of applying single-cell analyses in ageing research.

Frampton et al. review emerging understanding of how the three primary gut-derived short-chain fatty acids—acetate, propionate and butyrate—affect skeletal muscle metabolism and function.

Fructose, a monosaccharide derived from fruits, is primarily consumed in a form combined with glucose as sugar or as a component of high-fructose corn syrup added as a sweetener to processed foods and carbonated beverages. Increased consumption of fructose has emerged as a major contributor to non-alcoholic fatty liver disease, dyslipidaemia, insulin resistance and diabetes. Now Zhao et al. show that hepatic lipid synthesis is increased by fructose metabolism in both the liver and intestine.

Macrophages are required for postinjury skeletal muscle regeneration. A new study reveals that proinflammatory macrophages produce meteorin-like, which promotes muscle stem cell expansion through the Stat3–IGF1 axis and then shifts their inflammatory profile to allow return to homeostasis.

Childhood obesity is one of the most serious public-health challenges of this century. Here, Caprio et al. provide a Review encompassing several aspects of childhood obesity, including epidemiology, genetic and environmental contributions, and cardiometabolic complications.