Reviews & Analysis

Methionine restriction modulates tumour growth and ageing processes through its influence on diverse metabolic processes. Ji et al. demonstrate that methionine restriction compromises production of hydrogen sulfide (H₂S), which impairs H₂S-mediated immune signalling and results in increased cancer progression in immunocompetent mice.

Astrocytes are usually viewed as archetypical glycolytic cells. A study now shows that fatty acid oxidation in astrocytes rearranges the respiratory chain to a configuration that safeguards neuronal functionality and proper cognitive performance in mice.

Mao et al. discover that heart failure-associated metabolic derangement results in cardiomyocyte cholesterol overload and accumulation of bile acid intermediates, which in turn trigger mitochondrial damage and inflammatory activation and thus promote heart failure.

Impaired tricarboxylic acid cycle and oxidative phosphorylation cause reduced energy content in neurons upon neuroinflammation and contribute to axonal degeneration in multiple sclerosis.

Time-restricted eating, a form of intermittent fasting, has shown promise in promoting metabolic health. In mice, limiting food accessibility only to the active cycle reduces body weight and improves glucose homeostasis; now, Xin et al. show that restricting feeding to the resting period increases their running performance.

How photosynthetic microbes regulate CO₂ fixation and carbon metabolism in response to fluctuating environments is of fundamental and industrial relevance. In this issue, Lu et al. uncover a cryptic enzymatic function that accelerates the shutdown of the Calvin cycle under a transition into the dark.

Adipogenesis of adipose progenitor cells is considered metabolically beneficial. Two laboratories have simultaneously discovered that adipose progenitors also give rise to structural WNT-regulated adipose tissue-resident (SWAT) cells during adipogenesis to maintain the progenitor pool.

An elegant quantitative analysis of brown fat and skeletal muscle metabolite flux reveals unpredicted fuel usage during thermogenesis, which suggests that brown fat predominantly uses glucose and lactate and acts as a nitrogen scavenger.

Inflammation is characterized by cell metabolic reprogramming that can influence the outcome of metabolic syndrome-related diseases such as non-alcoholic fatty liver disease (NAFLD). In this issue, Weiss et al. discover that preventing the production of the immunomodulatory metabolite itaconate increases liver fat accumulation in mouse models of NAFLD and that treatment with itaconate may promote fat oxidation. This study reveals new therapeutic potential for targeting the itaconate metabolic pathway in NAFLD.

Post-ingestive signals of nutrient availability can drive food reward and neural responses independently of orosensory signals. van Galen et al. demonstrate that brain responses to these post-ingestive signals are impaired in people with obesity

Functional genomic analyses reveal a complex relationship between the COBLL1 gene and metabolic health, as well as how the same variant can both reduce body fat and increase the risk of type 2 diabetes.

How mammals enter hypometabolic states, known as torpor and hibernation, has fascinated researchers for decades, but the central control mechanisms that regulate entry into torpor have surfaced only recently. Yang and colleagues demonstrate that torpor-like hypometabolic states can be induced non-invasively by ultrasound, providing new routes for exploiting the underlying mechanisms and biomedical applications of this process in the future.

M⁶A RNA modifications mediate RNA processing and stability. Ceramides are lipid metabolites containing an amino acid-based backbone, which promote metabolic dysfunction. Wang et al. describe a novel m⁶A-dependent regulatory node that tunes ceramide-generating enzymes.

Glycolysis provides building blocks for the proinflammatory activation of macrophages and simultaneously generates pyruvate. In this issue of Nature Metabolism, Ran et al. provide evidence that the transport of pyruvate to fuel the Krebs cycle in the mitochondria is not required in the inflammatory response.

Most of human microbiome research has focused on analysing faecal samples, which represent the final stop of the digestive journey. Two recent articles use a novel sampling approach to capture luminal content at different points during digestion and reveal that the analysis of faecal samples tells only a fraction of the story.

In this issue of Nature Metabolism, a gut bacterial glucosidase that degrades the antidiabetic drug acarbose is linked to poor treatment response. Its widespread distribution in the human microbiome could compromise the efficacy of acarbose treatment in many patients.

A proteo-transcriptomic analysis of nonalcoholic fatty liver disease (NAFLD) uncovers biological pathways and potential biomarkers of high-risk disease. The work expands our understanding of the cellular origins of protein changes in NAFLD and translates them into an accurate diagnostic tool.

GAPDH is highly sensitive to oxidation by reactive oxygen species, but how exactly its oxidation alters carbon flux is not known. Talwar et al. demonstrate that oxidative inactivation of GAPDH is required for maximal pentose phosphate pathway flux to support NADPH generation during oxidative stress.

Diabetic kidney disease is influenced by a combination of genetic and environmental factors. A study identifies risk variants in the XOR promoter that elevate its own activity in response to hyperglycaemia, which has a causative role in the onset and progression of diabetic kidney disease.

Fatty acids generated through lipolysis are constantly re-esterified into triglycerides in what is known as the glyceride–fatty acid futile cycle. A recent quantification of the activity of this futile cycle in adipocytes suggests that it may have manifold implications for systemic energy homeostasis.