ArticleThe Journal of clinical investigation1997
Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.
Article in The Journal of clinical investigation, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02633488 (Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome), which is not on this map. Cited by 206 papers, 2 of them syntheses 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.
Effect of Metformin on Insulin Sensitivity and Pan-Arterial Vascular Function in Adults With Metabolic Syndrome
Who cites it
206 citing papers in PubMed, 2 syntheses or guidelines pooled it, 760 citations in OpenAlex.
- Impact of exercise dosages based on American College of Sports Medicine recommendations on lipid metabolism in patients after PCI: a systematic review and meta-analysis of randomized controlled trials.Lipids in health and disease · 2024Pooled it
- Pooled it
- The Role of Serum Free Fatty Acids in Endothelium-Dependent Microvascular Function.Endocrinology, diabetes & metabolism · 2025Trial
- Fat Consumption Attenuates Cortical Oxygenation during Mental Stress in Young Healthy Adults.Nutrients · 2023Trial
- Impact of Acipimox Therapy on Free Fatty Acid Efflux and Endothelial Function in the Metabolic Syndrome: A Randomized Trial.Obesity (Silver Spring, Md.) · 2019Trial
- Effect of Sacubitril/Valsartan on Exercise-Induced Lipid Metabolism in Patients With Obesity and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2018Trial
- Common variants associated with changes in levels of circulating free fatty acids after administration of glucose-insulin-potassium (GIK) therapy in the IMMEDIATE trial.The pharmacogenomics journal · 2017Trial
- Caloric restriction decreases orthostatic tolerance independently from 6° head-down bedrest.PloS one · 2015Trial
- Early microvascular recruitment modulates subsequent insulin-mediated skeletal muscle glucose metabolism during lipid infusion.Diabetes care · 2013 · on this mapTrial
- Vascular effects of intravenous intralipid and dextrose infusions in obese subjects.Metabolism: clinical and experimental · 2012Trial
- Flavanol-rich cocoa ameliorates lipemia-induced endothelial dysfunction.Heart and vessels · 2011Trial
- Free fatty acids induce insulin resistance in both cardiac and skeletal muscle microvasculature in humans.The Journal of clinical endocrinology and metabolism · 2011 · on this mapTrial
- Improvements in vascular health by a low-fat diet, but not a high-fat diet, are mediated by changes in adipocyte biology.Nutrition journal · 2011Trial
- Effects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects.American journal of physiology. Endocrinology and metabolism · 2010Trial
- Intravenous intralipid-induced blood pressure elevation and endothelial dysfunction in obese African-Americans with type 2 diabetes.The Journal of clinical endocrinology and metabolism · 2009Trial
- Selective PKC beta inhibition with ruboxistaurin and endothelial function in type-2 diabetes mellitus.Cardiovascular drugs and therapy · 2009Trial
- Aging and metabolism contribute separately to brain-body health.PLoS biology · 2026Article
- Cell apoptosis in ischemic stroke: Focus on lipid metabolism.Neural regeneration research · 2026Article
- Endothelial Metabolic Reprogramming Links Diabetes to Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Association Between Blood Free Fatty Acid Concentrations in Midlife and Cerebral Small Vessel Disease.Antioxidants (Basel, Switzerland) · 2025Article
146 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
8 authors at 2 institutions in 1 country.
Funding
Abstract
We have recently shown that insulin-resistant obese subjects exhibit impaired endothelial function. Here, we test the hypothesis that elevation of circulating FFA to levels seen in insulin-resistant subjects can impair endothelial function. We studied leg blood flow responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (Mch) or the endothelium-independent vasodilator sodium nitroprusside during the infusion of saline and after raising systemic circulating FFA levels exogenously via a low- or high-dose infusion of Intralipid plus heparin or endogenously by an infusion of somatostatin (SRIF) to produce insulinopenia in groups of lean healthy humans. After 2 h of infusion of Intralipid plus heparin, FFA levels increased from 562+/-95 to 1,303+/-188 micromol, and from 350+/-35 to 3,850+/-371 micromol (P < 0.001) vs. saline for both low- and high-dose groups, respectively. Mch-induced vasodilation relative to baseline was reduced by approximately 20% in response to the raised FFA levels in both groups (P < 0.05, saline vs. FFA, ANOVA). In contrast, similar FFA elevation did not change leg blood flow responses to sodium nitroprusside. During the 2-h SRIF infusion, insulin levels fell, and FFA levels rose from 474+/-22 to 1,042+/-116 micromol (P < 0.01); Mch-induced vasodilation was reduced by approximately 20% (P < 0.02, saline vs. SRIF, ANOVA). Replacement of basal insulin levels during SRIF resulted in a fall of FFA levels from 545+/-47 to 228+/-61 micromol, and prevented the impairment of Mch-induced vasodilation seen with SRIF alone. In conclusion, (a) elevated circulating FFA levels cause endothelial dysfunction, and (b) impaired endothelial function in insulin-resistant humans may be secondary to the elevated FFA concentrations observed in these patients.
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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 Socratic graph.