Volume 5 Issue 8, August 2023

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

Impaired tricarboxylic acid cycle and oxidative phosphorylation cause reduced energy content in neurons upon neuroinflammation and contribute to axonal degeneration in multiple sclerosis.

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.

Sensory association learning is impaired in people with insulin resistance but can be restored following a one-time intervention with liraglutide. These findings provide ample evidence for metabolic signals as modulators of adaptive behaviour and suggest a potential role for GLP-1 receptor agonists in obesity management.

By using a combination of transcriptomics, primary adipocyte culture and experimental medicine approaches, we identified the sodium-dependent serotonin transporter SERT as a novel regulator of human brown adipose tissue function.

Rosenbaum and Foster discuss the metabolic underpinnings of weight loss and weight loss maintenance, as well as the implications of considering them as distinct metabolic states for the treatment of obesity.

In this Review, TeSlaa, Ralser, Fan and Rabinowitz comprehensively review the fundamental biochemical aspects of the pentose phosphate pathway and discuss its biological relevance in the context of physiology and pathology.

In this study, Morant-Ferrando, Jiménez-Blasco et al. show that fatty acid oxidation in astrocytes is necessary to maintain a specific configuration of the electron transport chain, which enables controlled production of reactive oxygen species that fine-tune neuron–glia metabolic coupling and support cognitive function.

In this study, Vande Voorde et al. investigate the potential of untargeted metabolomics as a stratification tool for colorectal cancer (CRC). They present a comprehensive pipeline to uncover metabolic vulnerabilities in CRC based on its genetic origin. With this approach, they show perturbations in methionine metabolism linked to APC deficiency, and identify adenosylhomocysteinase as an actionable therapeutic target.

Suchacki et al. show that serotonin suppresses human brown adipose tissue (BAT) activation, and that inhibition of the serotonin transporter (SERT) potentiates the suppressive action of extracellular serotonin on BAT by preventing serotonin uptake.

Variants in the FTO gene locus are known to be associated with obesity, including rs1421085 T>C variant, and now it is shown in mouse knock-in models that this C-allele increases expression of the Fto gene in brown adipocytes and enhances brown adipose tissue thermogenesis and obesity resistance.

Hanssen et al. demonstrate that associative learning is reduced when metabolic sensing is impaired in obesity and can be restored by liraglutide.

In this study, Tai et al. provide insights into the metabolic and bioenergetic responses in the axonal compartment in the context of multiple sclerosis. Moreover, they show how upregulating the tricarboxylic acid cycle confers protection against neuroinflammation-induced energy deprivation.

Mao et al. show that deficiency in CRAT, a key determinant of metabolic flexibility, triggers type I interferon responses and AIM2 inflammasome activation by promoting the bile acid synthesis pathway in cardiomyocytes.

Huang et al. develop an interface to allow electrode-mediated stimulation of gene expression in human cells, utilizing direct current-generated reactive oxygen species to stimulate transgene expression downstream of the KEAP1–NRF2 biosensor. In a type 1 diabetic mouse model, this interface is demonstrated to ameliorate hyperglycemia by stimulating insulin expression.

In this study, Wang, Xu et al. investigate the interaction of neutrophils and T cells in lymphoid tissues away from the tumour area, and how metabolic competition between these immune cell populations impairs anti-tumour immunity in the context of breast cancer.

Gnanaprakasam et al. study the amino acid requirements during different phases of T cell activation and show how asparagine restriction imparts opposing effects during early and late phases of T cell maturation through an NRF2-dependent mechanism.