ArticleNature communications2021
Acetoacetate protects macrophages from lactic acidosis-induced mitochondrial dysfunction by metabolic reprograming.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Biomimetic stress granules replenish lysosomal repair to reinstate macrophage immunometabolic antibacterial programs.Bioactive materials · 2027Article
- Acetoacetate-GPR43 axis epigenetically silences IL-6/CSF1 to restrict TAMs-driven metastatic lung cancer.Journal of translational medicine · 2026Article
- Tri-modal nanocatalytic microenvironment regulations for macrophage reprogramming and osteoporotic fracture healing promotion.Materials today. Bio · 2026Article
- Methylcrotonyl-CoA carboxylase 2 supports leucine catabolism to promote mitochondrial biogenesis and alleviate cisplatin-induced acute kidney injury.Kidney research and clinical practice · 2026Article
- The value of targeting ketone body metabolism in inflammatory and autoimmune diseases.Journal of translational medicine · 2026Review
- Review
- Physiological responses to mask-associated COFrontiers in public health · 2026Review
- Vitexin enhances mitophagy and improves renal ischemia-reperfusion injury by regulating the p38/MAPK pathway.Renal failure · 2025Article
- Innovative polymer-based therapeutics targeting inflammation for responsive drug delivery in disease treatment.Inflammopharmacology · 2025Review
- Metabolic reprogramming of immune cells in the battle against intracellular bacterial chronic infections: novel mechanisms and breakthroughs.Molecular biology reports · 2025Review
- How lactate and lactylation shape the immunity system in atherosclerosis (Review).International journal of molecular medicine · 2025Review
- The crosstalk between immune activation and metabolism in heart failure. A scientific statement of the Heart Failure Association of the ESC.European journal of heart failure · 2025Review
- Ketogenic diet ameliorates MASLD via balancing mitochondrial dynamics and improving mitochondrial dysfunction.Nutrition & diabetes · 2025Article
- Peptide Drug: Design and Clinical Applications.MedComm · 2025Review
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- β-hydroxybutyrate inhibits Plasmodium falciparum development and confers protection against malaria in mice.Nature metabolism · 2025Article
- Comprehensive Overview of Ketone Bodies in Cancer Metabolism: Mechanisms and Application.Biomedicines · 2025Review
- Multisystem clinicopathologic and genetic analysis of MELAS.Orphanet journal of rare diseases · 2024Article
- SGLT2 inhibition alters substrate utilization and mitochondrial redox in healthy and failing rat hearts.The Journal of clinical investigation · 2024Article
- Mitochondrial metabolic reprogramming of macrophages and T cells enhances CD47 antibody-engineered oncolytic virus antitumor immunity.Journal for immunotherapy of cancer · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lactic acidosis, the extracellular accumulation of lactate and protons, is a consequence of increased glycolysis triggered by insufficient oxygen supply to tissues. Macrophages are able to differentiate from monocytes under such acidotic conditions, and remain active in order to resolve the underlying injury. Here we show that, in lactic acidosis, human monocytes differentiating into macrophages are characterized by depolarized mitochondria, transient reduction of mitochondrial mass due to mitophagy, and a significant decrease in nutrient absorption. These metabolic changes, resembling pseudostarvation, result from the low extracellular pH rather than from the lactosis component, and render these cells dependent on autophagy for survival. Meanwhile, acetoacetate, a natural metabolite produced by the liver, is utilized by monocytes/macrophages as an alternative fuel to mitigate lactic acidosis-induced pseudostarvation, as evidenced by retained mitochondrial integrity and function, retained nutrient uptake, and survival without the need of autophagy. Our results thus show that acetoacetate may increase tissue tolerance to sustained lactic acidosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.