Exposure to palmitic acid significantly reduced flow-induced dilation in human resistance arterioles compared with oleic acid (62% vs 69% maximal dilation; p=0.002) and increased ceramide production.
Does palmitic acid exposure impair microvascular endothelial function and increase ceramide production in human resistance arterioles and HUVECs?
Palmitic acid exposure impairs microvascular endothelial function and increases ceramide production via the de novo pathway, providing a mechanistic link between dietary saturated fat and cardiovascular risk.
Absolute Event Rate: 62% vs 69%
p-value: p=0.002
Background: Microvascular endothelial dysfunction, characterized by reduced nitric oxide (NO)-mediated flow-induced dilation, is an early marker of cardiovascular disease (CVD). Consumption of palmitic acid (PA), the most abundant saturated fatty acid in the United States diet, has been associated with increased risk of CVD, potentially via de novo ceramide synthesis that impairs microvascular endothelial function. The purpose of the study is to investigate the effect of PA exposure on microvascular endothelial function and whether the lipid is capable of increasing ceramide levels via the de novo pathway. We hypothesize that PA impairs microvascular endothelial function and increases ceramide production. Methods: Human resistance arterioles (80–250 µm) were isolated from adipose tissue obtained from otherwise healthy adults (0–1 risk factors for coronary artery disease). Vessels were treated with PA (500 µM, n=5, 16-20 hr) or oleic acid (OA; 500 µM, n=4, 16-20 hr), which served as a lipid control. Flow-induced dilation was assessed in isolated human microvessels using videomicroscopy. The nitric oxide synthase inhibitor L-NAME (100 µM; 30 minutes) was used to determine the contribution of NO to flow-induced dilation. In parallel experiments, human umbilical vein endothelial cells (HUVECs) were treated with PA (200 µM, n=3) or OA (200 µM, n=3) for 16-20 hr, and cellular ceramide levels were quantified using liquid chromatography-mass spectrometry. To verify involvement of the de novo ceramide synthesis pathway, cells were pretreated with myriocin (30 nM; serine palmitoyltransferase inhibitor) and fumonisin B1 (FB1, 30 µM; ceramide synthase inhibitor). Results: Vessels exposed to PA demonstrated a significant (p=0.002) reduction in flow-induced dilation compared with OA-treated control vessels. Importantly, PA-induced impairment of flow-induced dilation was not diminished by L-NAME (PA; 62±8 vs. PA+L-NAME; 77±7 % maximal dilation, p=0.001), indicating a loss of NO-dependent dilation. In contrast, flow-induced dilation in OA-treated vessels was significantly inhibited by L-NAME (OA; 69±7 vs. OA+L-NAME; 44±12 % maximal dilation, p=0.022), confirming preserved NO-mediated endothelial function. HUVECs treated with PA demonstrated significantly (p< 0.05) elevated levels of C16, C18, C20, C22, and C24:1 ceramide compared with OA-treated cells. Furthermore, ceramide levels in cells co-treated with PA and Myriocin or FB1 were markedly reduced (p< 0.05) than those in cells treated with PA. Conclusions: These findings suggest exogenous exposure to palmitic acid disrupts microvascular endothelial function and increases cellular ceramide production via the de novo pathway, providing a mechanistic link between dietary palmitic acid intake and elevated cardiovascular risk. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Simovic et al. (Fri,) conducted a other in Healthy adults (0-1 risk factors for coronary artery disease). Palmitic acid vs. Oleic acid was evaluated on Flow-induced dilation (p=0.002). Exposure to palmitic acid significantly reduced flow-induced dilation in human resistance arterioles compared with oleic acid (62% vs 69% maximal dilation; p=0.002) and increased ceramide production.