ArticleDiabetes2009
Muscle-derived angiopoietin-like protein 4 is induced by fatty acids via peroxisome proliferator-activated receptor (PPAR)-delta and is of metabolic relevance in humans.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
What it found
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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
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.
- The relationship between plasma angiopoietin-like protein 4 levels, angiopoietin-like protein 4 genotype, and coronary heart disease risk.Arteriosclerosis, thrombosis, and vascular biology · 2010Pooled it
- Fasting induces ANGPTL4 and reduces LPL activity in human adipose tissue.Molecular metabolism · 2020Trial
- Omega-3 long-chain fatty acids strongly induce angiopoietin-like 4 in humans.Journal of lipid research · 2013Trial
- Uncoupling protein 3 regulates energy and stress-related pathways in undifferentiated skeletal muscle myoblasts.American journal of physiology. Cell physiology · 2025Article
- Development of fatty acid analogues with potent anabolic effects on bone in male mice.Bone reports · 2025Article
- Gene expression dynamics in fibroblasts during early-stage murine pancreatic carcinogenesis.iScience · 2025Article
- Adipose Factor ANGPTL4: Its Role in Aging Mechanisms and Associated Diseases.Clinical interventions in aging · 2025Review
- Omega-3 fatty acid regulation of lipoprotein lipase and FAT/CD36 and its impact on white adipose tissue lipid uptake.Lipids in health and disease · 2024Review
- Association of antipsychotic drugs on type 2 diabetes mellitus risk in patients with schizophrenia: a population-based cohort and in vitro glucose homeostasis-related gene expression study.BMC psychiatry · 2024Article
- Article
- Fasting upregulates the monocarboxylate transporter MCT1 at the rat blood-brain barrier through PPAR δ activation.Fluids and barriers of the CNS · 2024Article
- Endothelial c-Myc knockout disrupts metabolic homeostasis and triggers the development of obesity.Frontiers in cell and developmental biology · 2024Article
- Pro-Calcifying Role of Enzymatically Modified LDL (eLDL) in Aortic Valve Sclerosis via Induction of IL-6 and IL-33.Biomolecules · 2023Article
- Article
- 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
- Histone Deacetylases as Modulators of the Crosstalk Between Skeletal Muscle and Other Organs.Frontiers in physiology · 2022Review
- A Review of free fatty acid-induced cell signaling, angiopoietin-like protein 4, and skeletal muscle differentiation.Frontiers in physiology · 2022Review
- Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveLong-chain fatty acids (LCFAs) contribute to metabolic homeostasis in part via gene regulation. This study's objective was to identify novel LCFA target genes in human skeletal muscle cells (myotubes). RESEARCH DESIGN AND
methodsIn vitro methods included culture and treatment of human myotubes and C2C12 cells, gene array analysis, real-time RT-PCR, Western blotting, ELISA, chromatin immunoprecipitation, and RNA interference. Human subjects (two cohorts) were characterized by oral glucose tolerance test, hyperinsulinemic-euglycemic clamp, magnetic resonance imaging and spectroscopy, and standard blood analyses (glucose, insulin, C-peptide, and plasma lipids).
resultsWe show here that ANGPTL4 (encoding angiopoietin-like protein 4) represents a prominent LCFA-responsive gene in human myotubes. LCFA activated peroxisome proliferator-activated receptor (PPAR)-delta, but not PPAR-alpha or -gamma, and pharmacological activation of PPAR-delta markedly induced ANGPTL4 production and secretion. In C2C12 myocytes, knockdown of PPARD, but not of PPARG, blocked LCFA-mediated ANGPTL4 induction, and LCFA treatment resulted in PPAR-delta recruitment to the ANGPTL4 gene. In addition, pharmacological PPAR-delta activation induced LIPE (encoding hormone-sensitive lipase), and this response crucially depended on ANGPTL4, as revealed by ANGPTL4 knockdown. In a human cohort of 108 thoroughly phenotyped subjects, plasma ANGPTL4 positively correlated with fasting nonesterified fatty acids (P = 0.0036) and adipose tissue lipolysis (P = 0.0012). Moreover, in 38 myotube donors, plasma ANGPTL4 levels and adipose tissue lipolysis in vivo were reflected by basal myotube ANGPTL4 expression in vitro (P = 0.02, both).
conclusionsANGPTL4 is produced by human myotubes in response to LCFA via PPAR-delta, and muscle-derived ANGPTL4 seems to be of systemic relevance in humans.
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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.