Volume 4 Issue 9, September 2022

The rapid increase in lipidomic data has triggered a community-based movement to develop guidelines and minimum requirements for generating, reporting and publishing lipidomic data. The creation of a dynamic checklist summarizing key details of lipidomic analyses using a common language has the potential to harmonize the field by improving both traceability and reproducibility.

Mass spectrometry imaging holds promise for mapping the intricate organization of metabolism in complex tissues. Wang et al. combine this exciting technique with metabolic tracing ex vivo to uncover metabolic specialization and adaptation in the mouse kidney.

It has long been recognized that some phenotypic variation in mammals cannot be explained by known genetic or environmental variables. Here, the authors show that the absence of Nnat expression is associated with polyphenism in mice with the same genotype. Broadly consistent effects are also found in humans.

Decreased insulin action and insulin receptor signalling contribute to the pathology of diabetes. Liu et al. uncover a role for the Ephrin type-B receptor 4 in insulin receptor degradation regulating liver and systemic insulin sensitivity.

PRDM16 is a key mediator of thermogenic fat, counteracting adipose fibrosis and inflammation. Kajimura and co-authors demonstrate that a CUL2–APPBP2 ubiquitin E3 ligase complex destabilizes the PRDM16 protein, resulting in declined metabolic activity in an age-dependent manner.

This Review summarizes emerging concepts for diabetes therapy aimed at specifically altering β cell biology and function, such as β cell insulin signalling, proliferation, differentiation, apoptosis, as well as the selective killing of senescent β cells.

Understanding dynamic metabolic changes in complex biological samples often overlooks heterogeneity in cell composition. Wang et al. combine mass spectrometry imaging, isotope tracing, and multiplexed immunofluorescence microscopy to study metabolic dynamics in the kidney upon ischemia–reperfusion.

Achreja et al. develop a framework to identify collateral lethalities in cancer, uncovering MTHFD2 as a collateral lethal gene in UQCR11-deficient ovarian tumours.

Synergistic toxicity of alcohol and cannabinoid exposure in mice leads to impairments on motor coordination by affecting the activity of presynaptic cannabinoid type 1 receptors and extrasynaptic glycine receptors in cerebellar Purkinje cells.

Yang et al. show that neuronatin (NNAT) can explain part of the phenotypic variation of complex traits, independently of genetics or the environment. Such NNAT-dependent variations can stratify human cohorts into four metabolic sub-types, including two distinct types of obesity.

Chen et al. show that the endoplasmic reticulum stress sensor IRE1α acts in white and beige adipocytes to restrain beige adipocyte activation, through regulation of lipolysis and Pgc1α messenger RNA levels, respectively.

Alterations in hepatic lipid metabolism may contribute to the onset of non-alcoholic fatty liver disease as well as other metabolic disorders. In this work, Zhou et al. identify orosomucoid 2 (ORM2) as a regulator of lipid homeostasis in the liver.

The tyrosine kinase receptor EphB4 is shown to interact with the insulin receptor to facilitate its endocytosis and degradation, thereby decreasing insulin signaling and promoting insulin resistance.