Acetyl-CoA carboxylase obstructs CD8+ T cell lipid utilization in the tumor microenvironment.

The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor-infiltrating T cells (TILs), hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control. However, endogenous TILs and unmodified cellular therapy products fail to sustain bioenergetics in tumors. We reveal that the solid TME imposes perpetual acetyl-coenzyme A (CoA) carboxylase (ACC) activity, invoking lipid biogenesis and storage in TILs that opposes FAO. Using metabolic, lipidomic, and confocal imaging strategies, we find that restricting ACC rewires T cell metabolism, enabling energy maintenance in TME stress. Limiting ACC activity potentiates a gene and phenotypic program indicative of T cell longevity, engendering T cells with increased survival and polyfunctionality, which sustains cancer control.

Detection of adulteration in Hydrastis canadensis (goldenseal) dietary supplements via untargeted mass spectrometry-based metabolomics.

Current estimates report that approximately 25% of U.S. adults use dietary supplements for medicinal purposes. Yet, regulation and transparency within the dietary supplement industry remains a challenge, and economic incentives encourage adulteration or augmentation of botanical dietary supplement products. Undisclosed changes to the dietary supplement composition could impact safety and efficacy; thus, there is a continued need to monitor possible botanical adulteration or mis-identification. Goldenseal, Hydrastis canadensis L. (Ranunculaceae), is a well-known botanical used to combat bacterial infections and digestive problems and is widely available as a dietary supplement. The goal of this study was to evaluate potential adulteration in commercial botanical products using untargeted metabolomics, with H. canadensis supplements serving as a test case. An untargeted ultraperformance liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis was performed on 35 H. canadensis commercial products. Visual inspection of the chemometric data via principal component analysis (PCA) revealed several products that were distinct from the main groupings of samples, and subsequent evaluation of contributing metabolites led to their confirmation of the outliers as originating from a non-goldenseal species or a mixture of plant materials. The obtained results demonstrate the potential for untargeted metabolomics to discriminate between multiple unknown products and predict possible adulteration.

Conventional and accelerated-solvent extractions of green tea (camellia sinensis) for metabolomics-based chemometrics.

Metabolomics has emerged as an important analytical technique for multiple applications. The value of information obtained from metabolomics analysis depends on the degree to which the entire metabolome is present and the reliability of sample treatment to ensure reproducibility across the study. The purpose of this study was to compare methods of preparing complex botanical extract samples prior to metabolomics profiling. Two extraction methodologies, accelerated solvent extraction and a conventional solvent maceration, were compared using commercial green tea [Camellia sinensis (L.) Kuntze (Theaceae)] products as a test case. The accelerated solvent protocol was first evaluated to ascertain critical factors influencing extraction using a D-optimal experimental design study. The accelerated solvent and conventional extraction methods yielded similar metabolite profiles for the green tea samples studied. The accelerated solvent extraction yielded higher total amounts of extracted catechins, was more reproducible, and required less active bench time to prepare the samples. This study demonstrates the effectiveness of accelerated solvent as an efficient methodology for metabolomics studies.