ArticleMolecular metabolism2017
Angiopoietin-like protein 4 is an exercise-induced hepatokine in humans, regulated by glucagon and cAMP.
Article in Molecular metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 59 citations in OpenAlex.
- Exerkine-Mediated Inter-Organ Crosstalk and Translational Perspectives in Metabolic Diseases.Current obesity reports · 2026Review
- Cross-Platform Transcriptomic Analysis of 40 Human and Rodent Skeletal Muscle Exerkines.Muscles (Basel, Switzerland) · 2026Review
- Exercise-responsive endocrine-metabolic mediators in diabetes and cardiometabolic disorders: a systematic scoping review and evidence map.Frontiers in endocrinology · 2026Article
- Exercise intensity modulates the human plasma secretome and interorgan communication.bioRxiv : the preprint server for biology · 2025Article
- Physical Activity, Exerkines, and Their Role in Cancer Cachexia.International journal of molecular sciences · 2025Review
- Adipose Factor ANGPTL4: Its Role in Aging Mechanisms and Associated Diseases.Clinical interventions in aging · 2025Review
- ANGPTL4-the Link Binding Lipid Metabolism and Inflammation.Current medicinal chemistry · 2025Review
- Postprandial exercise regulates tissue-specific triglyceride uptake through angiopoietin-like proteins.JCI insight · 2024Article
- Molecular insights of exercise therapy in disease prevention and treatment.Signal transduction and targeted therapy · 2024Review
- Exploring exercise-driven exerkines: unraveling the regulation of metabolism and inflammation.PeerJ · 2024Review
- Cdo1-Camkk2-AMPK axis confers the protective effects of exercise against NAFLD in mice.Nature communications · 2023Article
- Highlighting the idea of exerkines in the management of cancer patients with cachexia: novel insights and a critical review.BMC cancer · 2023Review
- Article
- Chrono-exercise: Time-of-day-dependent physiological responses to exercise.Sports medicine and health science · 2023Review
- The Potential of Exerkines in Women's COVID-19: A New Idea for a Better and More Accurate Understanding of the Mechanisms behind Physical Exercise.International journal of environmental research and public health · 2022Review
- ANGPTL4, IL-6 and TNF-α as regulators of lipid metabolism during a marathon run.Scientific reports · 2022Article
- Review
- Mitochondrial Dysfunction Plays Central Role in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2022Review
- State of Knowledge on Molecular Adaptations to Exercise in Humans: Historical Perspectives and Future Directions.Comprehensive Physiology · 2022Article
- GDF15 is an exercise-induced hepatokine regulated by glucagon and insulin in humans.Frontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveAngiopoietin-like protein-4 (ANGPTL4) is a circulating protein that is highly expressed in liver and implicated in regulation of plasma triglyceride levels. Systemic ANGPTL4 increases during prolonged fasting and is suggested to be secreted from skeletal muscle following exercise.
methodsWe investigated the origin of exercise-induced ANGPTL4 in humans by measuring the arterial-to-venous difference over the leg and the hepato-splanchnic bed during an acute bout of exercise. Furthermore, the impact of the glucagon-to-insulin ratio on plasma ANGPTL4 was studied in healthy individuals. The regulation of ANGPTL4 was investigated in both hepatic and muscle cells.
resultsThe hepato-splanchnic bed, but not the leg, contributed to exercise-induced plasma ANGPTL4. Further studies using hormone infusions revealed that the glucagon-to-insulin ratio is an important regulator of plasma ANGPTL4 as elevated glucagon in the absence of elevated insulin increased plasma ANGPTL4 in resting subjects, whereas infusion of somatostatin during exercise blunted the increase of both glucagon and ANGPTL4. Moreover, activation of the cAMP/PKA signaling cascade let to an increase in ANGPTL4 mRNA levels in hepatic cells, which was prevented by inhibition of PKA. In humans, muscle ANGPTL4 mRNA increased during fasting, with only a marginal further induction by exercise. In human muscle cells, no inhibitory effect of AMPK activation could be demonstrated on ANGPTL4 expression.
conclusionsThe data suggest that exercise-induced ANGPTL4 is secreted from the liver and driven by a glucagon-cAMP-PKA pathway in humans. These findings link the liver, insulin/glucagon, and lipid metabolism together, which could implicate a role of ANGPTL4 in metabolic diseases.
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