Volume 5 Issue 1, January 2023

Investigation of multi-omic changes and their effects on regulation of metabolic pathways confirm anaplerotic deficiencies in methylmalonic acidaemia, strengthening the need for future therapies aimed at replenishing intermediates of the tricarboxylic acid cycle.

Commensal bacteria in the gut and their metabolites modulate the tonus of cancer immunosurveillance. Mao, Huang et al. demonstrate that the anticancer effects of caloric restriction depend on the expansion of acetate-producing immunostimulatory Bifidobacterium bifidum.

Iron is a growth factor for many microbes, and its availability is critical for the course of infections. A new study uncovers a mechanism by which extracellular vesicles released by macrophages withdraw iron from the blood, thereby limiting iron access for bacteria and improving outcomes from sepsis.

Sepsis takes a severe toll in the heart and can in some instances induce irreversible dysfunction. Zhang et al. discover a subset of macrophages that protects the septic heart by removing inflammogenic material released by cardiomyocytes.

Intracellular trafficking of cholesterol is essential for its uptake, storage and export. In this issue of Nature Metabolism, Xiao et al. provide powerful evidence for the importance of hepatic GRAMD1/Aster transporters in maintaining systemic cholesterol homeostasis.

Human pluripotent stem cell-derived pancreatic islets (PSC-islets) hold promise in type I diabetes treatment, although their delivery is a challenge. We describe a new abdominal infusion transplantation protocol that enables the survival, maturation and maintenance of functional PSC-islets in diabetic monkeys.

Nicholls and Brand present a bioenergetic critique of the futile creatine cycle as a mechanism for UCP1-independent diet-induced thermogenesis in brown adipose tissue.

A new transplantation site in the abdomen, the subanterior rectus sheath, is shown to allow for functional maturation of stem-cell-derived islet cells and improved glycemic control in a proof-of-principle study involving four nonhuman primates.

In this study, Oaks and Patel et al. characterize the crosstalk between the pentose phosphate pathway and mitochondrial redox homeostasis in the context of aldose reductase and transaldolase deficiency and the contribution of pentose phosphate pathway mitochondria deregulation to the progression from cirrhosis to hepatocellular carcinoma.

Yang, Yan, Ma et al. provide a comprehensive lactylome analysis of hepatocellular carcinoma patients, and show that analysis of protein lactylation can help uncover mechanisms that couple metabolic flux with metabolic alterations in hepatocellular carcinoma.

The authors combine multi-layered omics with clinical and biochemical features from individuals affected with methylmalonic aciduria, a rare inherited disease affecting succinyl-CoA synthesis, revealing that anaplerotic rewiring is a targetable feature.

The authors show that caloric restriction increases the intestinal abundance of Bifidobacterium bifidum, which in turn blunts tumour development in mice.

Kuang, Dou et al. show that upon Salmonella Typhimurium infection in mice, macrophages release extracellular vesicles (EVs) that harbor iron-uptake receptors. By sequestering iron via a humoral mechanism, these EVs limit bacterial growth and thereby protect against infection.

Zhang et al. identify a unique population of cardiac-resident macrophages that could be a potential therapeutic strategy for sepsis-induced cardiomyopathy.

Grb10, an adaptor protein known to regulate insulin signalling, can interact with the leptin receptor for enhancement of leptin signalling in hypothalamic AgRP and POMC neurons in mice.

Xiao and Kennelly et al. show that Aster-mediated nonvesicular cholesterol transport in the liver regulates hepatic and systemic lipid homeostasis during fasting, as well as reverse cholesterol transport.