Volume 5 Issue 9, September 2023

Spatial metabolomics has matured and is driving innovation in mass spectrometry, metabolomics and spatial omics. With exciting discoveries, complementary capabilities and increasing accessibility, it has secured its place in the spatial biology toolbox, showing promise in biology, medicine and pharmacology.

Subcellular quantitative analysis has been a long-standing goal of mass spectrometry imaging, but was originally thought to be unattainable. However, recent advances have made organelle-level absolute quantification through mass spectrometry imaging a reality, thanks to the development of nano secondary ion mass spectrometry.

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.

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.

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.

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.

A mouse pancreatic islet atlas comprising over 300,000 single-cell transcriptomes was integrated from nine biologically diverse datasets to unify existing knowledge in the islet biology community. This interactively accessible resource reveals new insights into the molecular identity and plasticity of islet and β-cells across sex, life span and diabetes progression.

Mishra and Townsend present an overview of the regulation, function and plasticity of adipose tissue sensory nerves that are relevant for metabolic processes in health and disease.

In young women, brain insulin action enhances peripheral insulin sensitivity, but only during the follicular phase of the menstrual cycle. This effect is absent in the luteal phase, possibly due to hypothalamic insulin resistance.

Perszyk et al. identify the neural basis for odour-imagery ability and show that it indirectly predicts weight-gain susceptibility through a mechanism that is dependent on food-cue reactivity.

The authors uncover a brain-to-stomach signalling axis that communicates gastric dysfunction associated with stress.

The authors identify a role for GABRA5 neurons in the lateral hypothalamus for energy balance regulation. Inhibiting these neurons increases weight gain and lipid accumulation through a process dependent on astrocytic GABA release.

Dietary methionine restriction has been reported to protect from cancer. Ji et al. describe a cancer-promoting effect of methionine restriction mediated by gut microbiota-induced sulfur deficiency and suppression of antitumour immunity.

In this study, the anti-anginal drug ranolazine is found to sensitize BRAF inhibitor-resistant melanoma to targeted therapy and immunotherapy by rewiring fatty acid oxidation and the methionine salvage pathway.

Here Mukherjee et al. characterize the bidirectional communication between adipose tissue and ovarian cancer cells and show that adipocytes instruct cancer cells to divert glycolytic glycerol-3-phosphate towards lipid synthesis, thus promoting metastasis.

Longitudinal deep lipidome profiling reveals >800 lipid species, many of which are associated with health-to-disease transitions in diabetes, ageing and inflammation.

Dutta et al. show that impaired mitochondrial fatty acid synthesis (mtFAS) leads to neurodegeneration, increased ceramide levels and disturbed iron metabolism in flies and in fibroblasts from individuals with a mutation in an mtFAS enzyme.

This study reports the mouse islet atlas, a curated resource integrating scRNA-seq data of over 300,000 cells from nine datasets, covering pancreas development, homeostasis and disease states.