Cell Metabolism

Immune cells regulate circulating adipocyte extracellular vesicle levels in response to metabolic shifts Tiash et al. show that adipocyte extracellular vesicles (adipoEVs) increase in circulation with obesity in mice and humans. Slowed clearance of EVs by tissue-resident macrophages and increased adipoEV production in obesity shunts adipoEVs into circulation, where they are available to signal to other organs.

Online now: Immune cells regulate circulating adipocyte extracellular vesicle levels in response to metabolic shifts

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Isoform usage as a distinct regulatory layer driving nutrient-responsive metabolic adaptation Transcriptome modulation is essential for metabolic adaptation to nutrient environments. However, the role of isoform usage, a crucial transcriptome c…

One year ago, Li et al. demonstrated that isoform usage constitutes a distinct and dynamic regulatory layer in metabolic adaptation, which is compromised in obesity and aging. Now free to read:
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Starvation triggers an organismal adaptive response that is orchestrated by endocrine factors. One year ago, Long et al. identified a famsin-glucagon axis that relays gut-derived hormonal cues to systemic glucose homeostasis during fasting.
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Two Letters in our March issue offer complementary perspectives on the evolving role of New Approach Methodologies (NAMs) in cardiometabolic research. NAMs are important tools to complement, but not replace the use of animal models.

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Neutrophil-mediated anti-tumoral effects of caloric restriction Caloric restriction confers several benefits in cancer, but the underlying mechanisms are not understood. In this issue of Cell Metabolism, Gao et al. highlight a newly identified neutrophil-dependent...

Caloric restriction confers several benefits in cancer, but the underlying mechanisms are not understood. Read the Preview of Gao et al. from our March issue, highlighting a newly identified neutrophil-dependent pathway modulated by caloric restriction. www.cell.com/cell-metabol...

Why timing matters in MASLD: Late-day metabolic control Metabolic dysfunction-associated steatotic liver disease (MASLD) is traditionally viewed as a static consequence of chronic caloric excess and insulin resistance. In the work previewed here, MASLD ins...

MASLD is emerging as a disorder of time-of-day-dependent metabolic vulnerability, with reduced insulin availability and worsening multisystem insulin resistance in the evening compared to the morning. Read the Preview of the work by Marjot et al. in our March issue www.cell.com/cell-metabol...

Read our March issue online: www.cell.com/cell-metabol...
The cover depicts a wavering butterfly kite, symbolizing the injured septic lung, tethered to a ribbon-like intestinal tract illustrating ketogenic foods, microbiota, and azelaic acid production.

The S100A8/A9 complex promotes food intake and prevents adipose tissue loss during cancer cachexia in mice Gao et al. report that cancer cachexia disrupts energy balance by reducing food intake and body weight. They identify a hypothalamic S100A8/A9-C3 signaling pathway linking inflammation to adipose tissue loss and metabolic imbalance.

Online now: The S100A8/A9 complex promotes food intake and prevents adipose tissue loss during cancer cachexia in mice

Targeting microbiota-generated acetaldehyde to prevent progression of metabolic dysfunction-associated steatotic liver disease Tang et al. reveal that high sugar intake promotes MASLD progression via microbiota-produced acetaldehyde, which drives fibrosis through MMP7 upregulation. An engineered probiotic, Ligilactobacillus salivarius HAM, enhances acetaldehyde clearance and prevents liver fibrosis in preclinical models, offering a novel therapeutic approach.

Online now: Targeting microbiota-generated acetaldehyde to prevent progression of metabolic dysfunction-associated steatotic liver disease

Leptin enhances the intracellular thyroid hormone activation in skeletal muscle to boost energy balance (Cell Metabolism 37, 936–953.e1–e7; April 1, 2025)

Online now: Leptin enhances the intracellular thyroid hormone activation in skeletal muscle to boost energy balance

Neuroimmunometabolic co-evolution in the tumor micro- and macroenvironment Zhang et al. provide a comprehensive overview of how cancer co-opts the central and peripheral nervous system to regulate local and systemic metabolic process and immune cell functions, affecting progression and treatment resistance. They identify knowledge gaps, propose strategies to address current limitations, and discuss clinically actionable neuroimmune and neurometabolic therapies.

Online now: Neuroimmunometabolic co-evolution in the tumor micro- and macroenvironment

Purified diets enable experimental rigor through compositional control in animal research Purified diets offer compositionally defined platforms that improve causal inference in nutrition studies. When aligned with the biological question, they enable targeted nutrient loss- and gain-of-function experiments, systematic lipid-source swaps, and the discovery of diet-microbiome-drug interactions. We recommend complementary validation in grain-based chow or human-relevant diets to maximize translational relevance.

Online now: Purified diets enable experimental rigor through compositional control in animal research

Scientific value and limitations of purified diets in animal research Purified diets widely used in rodent studies lack bioactive compounds from whole foods that affect gut microbiota and host physiology; this may cause contradictory outcomes in some studies. Prioritizing biological relevance over compositional reproducibility and reassessing dietary models are crucial for improving scientific rigor.

Online now: Scientific value and limitations of purified diets in animal research

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Excited to hear @nataliekrahmer.bsky.social discuss "Elucidating the cell architecture of metabolic liver disease" at Cell Press Symposia #CSMito2026 (June 21–23, 2026, Glasgow, Scotland)
Submit an abstract before March 9 to join her: http://dlvr.it/TRBjsD

Microbial-derived 3-phenylpropionic acid orchestrates immune-progenitor cell crosstalk to promote beige adipogenesis and energy expenditure The role of gut microbial metabolites in adapting to cold environments is not well understood. Li et al. reveal that cold-induced expansion of P. copri produces 3-PPA, which activates an immune-adipocyte progenitor axis to drive beige fat formation and combat obesity across species.

Online now: Microbial-derived 3-phenylpropionic acid orchestrates immune-progenitor cell crosstalk to promote beige adipogenesis and energy expenditure

Lack of PCK1 in hepatic stellate cells causes liver fibrosis by fueling tricarboxylic acid cycle and increasing glycolysis This study shows that a key metabolic enzyme, PCK1, protects the liver from scarring by keeping fibrogenic cells in a quiescent state. When PCK1 is reduced, these cells undergo metabolic reprogramming characterized by increased glycolysis, become aberrantly activated, and promote liver fibrosis in mice.

Online now: Lack of PCK1 in hepatic stellate cells causes liver fibrosis by fueling tricarboxylic acid cycle and increasing glycolysis

Modeling lipid homeostasis using stable isotope tracing and flux analysis Wessendorf-Rodriguez et al. develop a pipeline for applying metabolic flux analysis to quantify lipid homeostasis. Lipid-MFA elucidates differences in synthesis and salvage fluxes in precision-cut lung slices harboring tumors with common driver mutations of lung adenocarcinoma. Application of Lipid-MFA reveals distinct trafficking of ceramide species into the sphingolipidome.

Online now: Modeling lipid homeostasis using stable isotope tracing and flux analysis

Red blood cells serve as a primary glucose sink to improve glucose tolerance at altitude Martí-Mateos et al. show that red blood cells explain improved glucose tolerance at high altitude. By manipulating red blood cell number, they determine that these cells are necessary and sufficient for hypoxic hypoglycemia. This highlights red blood cells as unappreciated glucose regulators and reveals novel strategies to treat diabetes.

Online now: Red blood cells serve as a primary glucose sink to improve glucose tolerance at altitude

16-h fasting optimizes cancer immunotherapy in mice and humans Chen et al. show that a 16-h fasting regimen optimizes cancer immunotherapy. Fasting induces metabolic trade-offs in tumor cells, increasing intratumoral isoleucine. This nutrient fuels CD8+ T cell cytotoxicity via acetyl-CoA-driven epigenetic and lipid reprogramming. Clinically, this short-term fasting regimen enhances the anti-tumor efficacy of neoadjuvant immunotherapy in patients with colorectal cancer.

Online now: 16-h fasting optimizes cancer immunotherapy in mice and humans

Lipid droplet-induced T cell death sustains autoimmune tissue inflammation Kumar et al. identify a metabolically controlled trait of CD4+ T cells in autoimmune disease. Exposed to fatty acids in rheumatoid joints, they form lipid droplets containing pore-forming gasdermin D and its activator zDHHC5. These droplets induce plasma membrane lysis, resulting in the leakage of intracellular contents and tissue inflammation.

Online now: Lipid droplet-induced T cell death sustains autoimmune tissue inflammation

Deletion of Mfn2 in endothelial cells triggers a mitohormetic response that improves systemic metabolism and healthspan in mice Chivite et al. show that the genetic inactivation of the mitochondrial fusion protein MFN2 in the endothelium triggers a protective stress response that boosts fat burning, increases secretion of the hormone GDF15, and protects mice from obesity and age-related physical and cognitive decline.

Online now: Deletion of Mfn2 in endothelial cells triggers a mitohormetic response that improves systemic metabolism and healthspan in mice

Potential roles of unmeasured spectra and light’s frequency-dependent neural modulation in daylight-mediated metabolic improvements Wu et al. highlight unmeasured spectra (e.g., NIR) and light’s frequency-dependent neural modulation as key factors underlying daylight’s metabolic benefits, guiding future lighting and metabolic disease research.

Online now: Potential roles of unmeasured spectra and light’s frequency-dependent neural modulation in daylight-mediated metabolic improvements

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Want to be part of a meeting where every dimension of mitochondrial biology comes together — from metabolism & genetics to disease & therapy?

Submit an abstract to @CellSymposia #CSMito2026 for the opportunity to see the whole field at once!
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New approach methodologies: Don’t throw the baby out with the bathwater The NIH has recently called for expanding use of new approach methodologies (NAMs) to reduce use of animals in research. Arany discusses the need not to forget the irreplaceable aspects of animal research and their fundamental importance to biomedical advancement.

Online now: New approach methodologies: Don’t throw the baby out with the bathwater

NAMing the challenges and opportunities of new approach methodologies for studying cardiovascular metabolism This letter evaluates the use of new approach methodologies (NAMs), such as human-based in vitro and in silico platforms, to reduce, refine, or replace reliance on animal testing, and to enhance our understanding of cardiovascular metabolism.

Online now: NAMing the challenges and opportunities of new approach methodologies for studying cardiovascular metabolism

Semaglutide ameliorates osteoarthritis progression through a weight loss-independent metabolic restoration mechanism Qin et al. demonstrated the chondroprotective effects of semaglutide in obesity-related osteoarthritis. Mechanistically, these effects are independent of body weight loss and involve metabolic reprogramming of chondrocyte via the GLP-1R-AMPK-PFKFB3 signaling axis.

Online now: Semaglutide ameliorates osteoarthritis progression through a weight loss-independent metabolic restoration mechanism

Compartmentalized branched-chain amino acid metabolism orchestrates colorectal cancer dissemination via an UMP-vimentin axis Compartmentalized BCAA metabolism regulates CRC dissemination through UMP-mediated stabilization of vimentin, leading to pro-migrative traits. Targeting of BCAA metabolism by dietary restriction or repurposing of UMP biosynthesis inhibitors arrests CRC dissemination. Compartmentalized BCAA metabolism is a pan-cancer biomarker for poor survival. Our study thus links metabolic reprogramming to CRC metastasis.

Online now: Compartmentalized branched-chain amino acid metabolism orchestrates colorectal cancer dissemination via an UMP-vimentin axis

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Don't miss your chance to present your research at Cell Symposia: Multifaceted mitochondria in Glasgow, Scotland, June 21–23, 2026.

📆 Submit before Feb 13!
🔗 http://dlvr.it/TQmrlq

Ketogenic diet alleviates septic lung injury via microbial gut-lung axis Wei et al. show that a ketogenic diet protects against sepsis-induced lung injury via a gut-lung axis. Specific gut lactobacilli convert dietary oleic acid into azelaic acid, which translocates to the lung, promotes efferocytosis via PPAR-γ-mediated expansion of MerTK+ macrophages, and correlates with improved clinical outcomes in patients.

Online now: Ketogenic diet alleviates septic lung injury via microbial gut-lung axis