Trial reportDiabetologia2014
A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle.
Trial report in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01740817 (A Randomized, Crossover Study to Evaluate the Effect of Lipid Infusion on TLR4 Signaling and Insulin Resistance in Human Muscle), which is not on this map. Cited by 20 papers.
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.
A Randomized, Crossover Study to Evaluate the Effect of Lipid Infusion on TLR4 Signaling and Insulin Resistance in Human Muscle
Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Acute effects of physical exercise on the serum insulin-like growth factor system in women with fibromyalgia.BMC musculoskeletal disorders · 2017Trial
- Comparative Metabolomic Profiling of L-Histidine and NEFA Treatments in Bovine Mammary Epithelial Cells.Animals : an open access journal from MDPI · 2024Article
- Review
- Flunixin Meglumine Reduces Milk Isoprostane Concentrations in Holstein Dairy Cattle Suffering from Acute Coliform Mastitis.Antioxidants (Basel, Switzerland) · 2021Article
- Tankyrase inhibition ameliorates lipid disorder via suppression of PGC-1α PARylation in db/db mice.International journal of obesity (2005) · 2020Article
- Article
- Sphingolipid changes do not underlie fatty acid-evoked GLUT4 insulin resistance nor inflammation signals in muscle cells.Journal of lipid research · 2018Article
- Silica nanoparticles trigger hepatic lipid-metabolism disorder in vivo and in vitro.International journal of nanomedicine · 2018Article
- Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4.PloS one · 2018Article
- A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects.PloS one · 2018Article
- Methionine sulfoxide reductase B1 deficiency does not increase high-fat diet-induced insulin resistance in mice.Free radical research · 2017Article
- Intramyocellular ceramides and skeletal muscle mitochondrial respiration are partially regulated by Toll-like receptor 4 during hindlimb unloading.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Weight loss reduces basal-like breast cancer through kinome reprogramming.Cancer cell international · 2016Article
- Stress and inflammatory gene networks in bovine liver are altered by plane of dietary energy during late pregnancy.Functional & integrative genomics · 2015Article
- Lipid-mediated muscle insulin resistance: different fat, different pathways?Journal of molecular medicine (Berlin, Germany) · 2015Review
- MyD88 regulates physical inactivity-induced skeletal muscle inflammation, ceramide biosynthesis signaling, and glucose intolerance.American journal of physiology. Endocrinology and metabolism · 2015Article
- Lipid-induced insulin resistance does not impair insulin access to skeletal muscle.American journal of physiology. Endocrinology and metabolism · 2015Article
- Fetuin-A: a novel link between obesity and related complications.International journal of obesity (2005) · 2015Review
- Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.PloS one · 2015Article
- Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisInsulin-sensitive tissues (muscle, liver) of individuals with obesity and type 2 diabetes mellitus are in a state of low-grade inflammation, characterised by increased Toll-like receptor (TLR) expression and TLR-driven signalling. However, the cause of this mild inflammatory state is unclear. We tested the hypothesis that a prolonged mild increase in plasma NEFA will increase TLR expression and TLR-driven signalling (nuclear factor κB [NFκB] and mitogen-activated kinase [MAPK]) and impair insulin action in muscle of lean healthy individuals.
methodsTwelve lean, normal-glucose-tolerant participants were randomised to receive a 48 h infusion (30 ml/h) of saline or Intralipid followed by a euglycaemic-hyperinsulinaemic clamp. Vastus lateralis muscle biopsies were performed before and during the clamp.
resultsLipid infusion impaired insulin-stimulated IRS-1 tyrosine phosphorylation and reduced peripheral insulin sensitivity (p < 0.01). The elevation in circulating NEFA increased expression of TLR3, TLR4 and TLR5, and several MAPK (MAPK8, MAP4K4, MAP2K3) and inhibitor of κB kinase-NFκB (CHUK [IKKA], c-REL [REL] and p65 [RELA, NFKB3, p65]) signalling genes (p < 0.05). The lipid infusion also increased extracellular signal-regulated kinase (ERK) phosphorylation (p < 0.05) and tended to reduce the content of inhibitor of kappa Bα (p = 0.09). The muscle content of most diacylglycerol, ceramide and acylcarnitine species was unaffected. In summary, insulin resistance induced by prolonged low-dose lipid infusion occurs together with increased TLR-driven inflammatory signalling and impaired insulin-stimulated IRS-1 tyrosine phosphorylation. CONCLUSIONS/
interpretationA sustained, mild elevation in plasma NEFA is sufficient to increase TLR expression and TLR-driven signalling (NFκB and MAPK) in lean individuals. The activation of this pathway by NEFA may be involved in the pathogenesis of insulin resistance in humans.
trial registrationClinicalTrials.gov NCT01740817.
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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.