Calubag et al. report that reduced dietary intake of the branched-chain amino acid valine is sufficient to improve healthspan in both male and female mice, as well as to extend lifespan in male mice.

Abstract. Despite the success of endocrine therapy (ET) in treating hormone receptor-positive breast cancer, a significant proportion of patients relapse during or after treatment, making ET resistanc...

Leveraging pythons as an extreme model of feeding and fasting behaviour, this study uncovers para-tyramine-O-sulphate as a conserved postprandial metabolite that links nutrient intake to energy balanc...

Cell metabolism is a dynamic network of highly interconnected biochemical reactions. In this issue of Nature Metabolism, time-lapse analysis of the amino acid aspartate revealed an unexpected regulati...

Metastasis-associated oncofetal cell states emerge at the earliest stages of colorectal cancer and spatial profiling shows stereotypic patterning of fibroblast subtypes resembling normal tissue archit...

Circadian clock in adipocytes maintains metabolic health by regulating mitochondrial complex I respiration.

Nature Metabolism, Published online: 03 April 2026; doi:10.1038/s42255-026-01491-2This study demonstrates that overexpression of irisin, an exercise-induced myokine, ameliorates obesity and insulin resistance in high-fat-diet-fed mice by increasing local IL-33 production and preserving ST2+ regulatory T cells in white adipose tissues.

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Cytarabine is a key therapy for acute myeloid leukaemia (AML), but its efficacy is limited by the dNTPase SAMHD1, which hydrolyses its active metabolite. Screening nucleotide biosynthesis inhibitors ...

Beyond its traditional role in supporting bioenergetic and biosynthetic demands, the canonical TCA cycle is also essential for nutrient clearance. When pyruvate oxidation and citrate production increase, aconitase 2 becomes essential to prevent mitochondrial citrate accumulation, which can trigger the integrated stress response and impair cell fitness.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

CRISPR–Cas9 screening identifies CLCC1 as a factor that increases neutral lipid flux to prevent hepatic steatosis and promotes nuclear pore complex assembly by promoting membrane bending and fusi...

The authors present a genetically encoded tool based on a bifunctional enzyme that can regenerate NAD+ while executing an engineered glycerol shunt. The tool successfully restored redox imbalance and ...

Scientific papers are more complex than ever, but are we gaining deeper understanding or losing sight of the hypothesis? In this third part of Thinking like a scientist, I reflect on data-driven scien...

Obesity is a major disease risk factor due to obesity-associated hyperinflammation. We found that obesity induced Nod-like receptor pyrin domain–containing 3 (NLRP3) inflammasome hyperactivation and e...

Rathmell and colleagues show that metabolic reprograming of regulatory T cells is associated with severity of critical illness in patients with and without sepsis.

Diet and cancer Dual impacts of serine/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation Tong et al, Zhen Lei Hubing Shi ∙ Xuelei Ma. Dietary restriction…

People with Citrin Deficiency (CD), inactivated for both copies of SLC25A13 , have lean metabolic dysfunction-associated steatotic liver disease (MASLD) and an aversion to sweets. The mouse model of C...

FSP1 is a key suppressor of lipid peroxidation and ferroptosis, yet it is largely dispensable in standard cell culture models. Two new studies now show that FSP1 becomes essential for tumour growth in...

Nature Metabolism, Published online: 05 December 2025; doi:10.1038/s42255-025-01410-xA machine-learning-based computational approach to probe pathway coessentiality reveals that complex II of the electron transport chain regulates de novo purine synthesis, and can be targeted to treat acute myeloid leukaemia.

A fin-like structural loop in GPX4 is critical for anchoring the enzyme to cellular membranes, thereby preventing ferroptosis. A patient-associated R152H mutation destabilizes this loop, leading to fe...

In a recent Nature article, Xiao et al. report development of a metabolite-protein covariation architecture (MPCA) database from a diversity outbred mouse cohort that facilitates the deciphering of metabolite-protein relationships in liver and brown adipose tissue (BAT). Using these correlations, the authors describe a role for LRRC58 in controlling cysteine-taurine metabolism.

Human plasma-like medium (HPLM), a synthetic physiologic medium containing over 60 metabolites and small ions at concentrations reflective of adult human plasma, enhances the structural and metabolic....

Inherited mitochondrial DNA mutations can result in diverse clinical phenotypes. Here, the authors characterise a heteroplasmic tRNAAla mutation (m.5019A>G) in mice and demonstrate that macrophages...

A uridine-sensitized CRISPR-Cas9 screening identifies demethoxy-CoQ as an alternative electron acceptor in the absence of CoQ, and NUDT5 as a regulator of de novo pyrimidine synthesis via its interact...

Cells generate purine nucleotides through de novo purine biosynthesis (DNPB) and purine salvage. Purine salvage represses DNPB to prevent excessive purine nucleotide synthesis through mechanisms that ...

Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic depende...

Cells generate purine nucleotides through de novo purine biosynthesis (DNPB) and purine salvage. Purine salvage represses DNPB to prevent excessive purine nucleotide synthesis through mechanisms that ...

Live-cell imaging of mRNA encoding secretome proteins and translated nascent peptide markers show that secretome translation occurs at endoplasmic reticulum junctions near lysosomes, requires lun...

Targeting FSP1 in lymph nodes has considerable potential for blocking melanoma progression.

Second part of Thinking like a Scientist, reflecting on how genome editing and multi-omics, while powerful, can introduce conceptual flaws that distort our understanding of gene function and biologica...