ArticleNature metabolism2022
The aldolase inhibitor aldometanib mimics glucose starvation to activate lysosomal AMPK.
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Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed, 89 citations in OpenAlex.
- Trial
- AMPK activation by Aldometanib from Bigujing improves metabolic and cognitive dysfunction in aging mice.Metabolic brain disease · 2026Article
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- An epigenetic switch in β-cells links mitochondrial stress to inflammatory fate via HMGB1 acetylation.Cell death and differentiation · 2026Article
- circZNF148 Drives Glucose Metabolism Reprogramming to Enhance Metastasis and Immune Evasion via HK1 Stabilization in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanisms and therapeutic potential of AMPK signaling pathway in the regulation of lipid metabolism.Molecular biology reports · 2026Review
- Research and application advances in real-time single-cell functional analysis.Discover nano · 2026Review
- Illuminating compartmentalized AMPK signaling in single cells.The Biochemical journal · 2026Review
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- Lactate-activated GPR81/FARP1 signaling drives insulin-independent glucose uptake and metabolic control.Cell research · 2026Article
- ALDOA-Mediated Metabolic Reprogramming is a Targetable Vulnerability for Ferroptosis Sensitization in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Therapeutic targeting of the AMPK-Has1 complex formation ameliorates metabolic dysfunction-associated steatohepatitis in mice.Theranostics · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Glucose starvation mimetic aldometanib removes immune barriers permitting mice with hepatocellular carcinoma to live to normal ages.Cell research · 2025Article
- Oligodendrocyte precursor cell-specific blocking of low-glucose-induced activation of AMPK ensures myelination and remyelination.Nature metabolism · 2025Article
- Metformin and Adipose Tissue: A Multifaceted Regulator in Metabolism, Inflammation, and Regeneration.Endocrinology and metabolism (Seoul, Korea) · 2025Review
- Glucose metabolism and its direct action in cancer and immune regulation: opportunities and challenges for metabolic targeting.Journal of biomedical science · 2025Review
- Taurine Attenuates Disuse Muscle Atrophy Through Modulation of the xCT-GSH-GPX4 and AMPK-ACC-ACSL4 Pathways.Antioxidants (Basel, Switzerland) · 2025Article
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Authors and funding
45 authors at 4 institutions in 1 country.
Chen-Song Zhang *State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.ORCID http://orcid.org/0000-0001-5218-0101
Mengqi Li *State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.ORCID http://orcid.org/0000-0002-1171-5648
Yu Wang *State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Xiaoyang Li *State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Yue Zong *State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Shating LongState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Mingliang ZhangDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Jin-Wei FengState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Xiaoyan WeiState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Yan-Hui LiuState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Baoding ZhangState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Jianfeng WuLaboratory Animal Research Centre, Xiamen University, Fujian, China.
Cixiong ZhangState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Wenhua LianState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Teng MaState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Xiao TianState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Qi QuState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Yaxin YuState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Jinye XiongState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Dong-Tai LiuState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.ORCID http://orcid.org/0000-0002-7293-9717
Zhenhua WuState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Mingxia ZhuState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.ORCID http://orcid.org/0000-0002-1858-5655
Changchuan XieState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.ORCID http://orcid.org/0000-0002-1078-0464
Yaying WuState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Zheni XuState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.ORCID http://orcid.org/0000-0001-7926-0259
Chunyan YangState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Junjie ChenAnalysis and Measurement Centre, School of Pharmaceutical Sciences, Xiamen University, Fujian, China.
Guohong HuangState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Qingxia HeKey Laboratory of Ministry of Education for Protein Science, School of Life Sciences, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0001-8340-7305
Xi HuangState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Lei ZhangState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Xiufeng SunState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Qingfeng LiuState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Abdul GhafoorState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Fu GuiState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.ORCID http://orcid.org/0000-0001-8329-7118
Kaili ZhengState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Fujian, China.
Wen WangCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Liaoning, China.ORCID http://orcid.org/0000-0003-0986-8853
Zhi-Chao WangCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Liaoning, China.
Yong YuState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.
Qingliang ZhaoState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Fujian, China.
Shu-Yong LinState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China.ORCID http://orcid.org/0000-0002-4419-1713
Zhi-Xin WangKey Laboratory of Ministry of Education for Protein Science, School of Life Sciences, Tsinghua University, Beijing, China.
Hai-Long PiaoCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Liaoning, China.ORCID http://orcid.org/0000-0001-7451-0386
Xianming DengState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China. xmdeng@xmu.edu.cn.ORCID http://orcid.org/0000-0002-9354-5864
Sheng-Cai LinState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Fujian, China. linsc@xmu.edu.cn.ORCID http://orcid.org/0000-0003-1993-8376
Xiamen University · CNDalian Institute of Chemical Physics · CNShanghai Jiao Tong University · CNTsinghua University · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activity of 5'-adenosine monophosphate-activated protein kinase (AMPK) is inversely correlated with the cellular availability of glucose. When glucose levels are low, the glycolytic enzyme aldolase is not bound to fructose-1,6-bisphosphate (FBP) and, instead, signals to activate lysosomal AMPK. Here, we show that blocking FBP binding to aldolase with the small molecule aldometanib selectively activates the lysosomal pool of AMPK and has beneficial metabolic effects in rodents. We identify aldometanib in a screen for aldolase inhibitors and show that it prevents FBP from binding to v-ATPase-associated aldolase and activates lysosomal AMPK, thereby mimicking a cellular state of glucose starvation. In male mice, aldometanib elicits an insulin-independent glucose-lowering effect, without causing hypoglycaemia. Aldometanib also alleviates fatty liver and nonalcoholic steatohepatitis in obese male rodents. Moreover, aldometanib extends lifespan and healthspan in both Caenorhabditis elegans and mice. Taken together, aldometanib mimics and adopts the lysosomal AMPK activation pathway associated with glucose starvation to exert physiological roles, and might have potential as a therapeutic for metabolic disorders in humans.
Indexed as
InsulinsStarvationAdenosine MonophosphateAdenosine TriphosphatasesAMP-Activated Protein KinasesAnimalsCaenorhabditis elegansFructoseFructose-Bisphosphate AldolaseGlucoseHumansLysosomesMaleMiceAdenosine MonophosphateAdenosine TriphosphatasesAMP-Activated Protein KinasesFructoseFructose-Bisphosphate AldolaseGlucoseInsulins
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