News & Views in 2023

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.

Although astrocytes are largely glycolytic, they catabolize a variety of substrates via oxidative phosphorylation in the mitochondria. In this issue, Mi et al. show that oxidative phosphorylation in astrocytes protects the brain from inflammation and degeneration by degrading excess fatty acids.

Animals need to be able to evaluate environmental pH. Mechanisms that mediate sour taste and acid sensing have been reported across species, but less is known about the detection of high pH. Mi et al. identify the gene alkaliphile, which encodes a high-pH-gated chloride channel in the gustatory system of flies.

Defective nicotinamide adenine dinucleotide (NAD⁺) metabolism is involved in various diseases. A study in Nature Metabolism identifies the cytosolic mitochondrial-RNA sensing system as a mediator that links NAD⁺ deficiency to kidney disease in humans and mice.

Both cell cycle arrest and secretions of senescent cells are subject to metabolic control. In this issue of Nature Metabolism, Roh et al. show that lysosomal partitioning of cholesterol potentiates inflammatory secretion during senescence.

By measuring protein abundance in blood using high-throughput antibody-based techniques, a genetic map of blood proteins in humans replicates findings from much larger studies, uncovers hundreds of new signals and bridges genetic variation to multiple diseases.