News & Views

As most studies on the action of insulin in the brain have focused on men, metabolic changes during the menstrual cycle in women remain poorly understood. Using intranasal insulin administration during hyperinsulinaemic–euglycaemic clamps and functional MRI, Hummel et al. show reduced insulin sensitivity during the luteal phase.

Sa et al. identified a distinct neuronal subpopulation that controls brown adipose tissue thermogenesis. In mice fed a high-fat diet, hypothalamic GABRA5 neurons are deactivated by GABA released by surrounding astrocytes and inhibition of GABA synthesis ameliorates diet-induced obesity.

Okreglak et al. explore the molecular mechanisms that link organellar pH dynamics with the cell cycle, and find that vacuolar pH oscillates during cell cycle phases to ensure an adequate supply of amino acids during cell division. This study offers metabolic insight into the fundamental mechanisms that couple amino acid availability to the cell cycle through pH fluctuations.

In this issue of Nature Metabolism, a study shows that glutarate increases memory T cells as well as T cell cytotoxicity and reduces tumour growth. During T cell activation, glutarate levels and glutarylation increase. Glutarate inhibits α-ketoglutarate-dependent dioxygenases, and glutarylation reduces pyruvate dehydrogenase complex activity and enhances glycolysis.

The relationship between stress and gastrointestinal function is poorly understood and of major clinical importance as a potential contributor to irritable bowel syndrome, functional dyspepsia and numerous other disorders of gut–brain interaction. A recent study investigates a descending neural circuit that regulates gastric motility and is inversely modulated by chronic versus acute stress.

By combining multimodal metabolomics technologies to investigate colorectal tissues and tumours in situ, Vande Voode et al. found tumour genotype-specific metabolic profiles and revealed the methionine-cycle enzyme AHCY to be a potential therapeutic target in colorectal cancer.

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.