Oxytocin Attenuates Atherosclerosis and Adipose Tissue Inflammation in Socially Isolated ApoE−/− Mice

Abstract

Objective To determine the effect of exogenous oxytocin (OT) administration on inflammation and atherosclerosis in socially isolated apoE−/− mice. Hyperlipidemic animals housed in isolated or stressful social environments display more extensive atherosclerosis than those in an affiliative social environment. The neurohypophyseal peptide OT may be involved in both affiliative social behavior and cardiovascular homeostasis, suggesting a role in mediating the benefits of positive social interactions on atherosclerosis. Methods A total of 43, 12-week-old, apoE−/− mice were surgically implanted with osmotic minipumps containing OT (n = 23) or vehicle (n = 20). Blood samples were taken at baseline and after 6 weeks and 12 weeks of treatment. After 12 weeks of treatment, animals were killed, and samples of adipose tissue were dissected from a subset of OT-treated (n = 12) and vehicle-treated (n = 12) animals and incubated in culture media for 6 hours. Media samples were analyzed for interleukin (IL)-6 concentration corrected by sample dry weight. Aortas were dissected, formalin-fixed, and stained with oil-red O for en face quantification of lesion area. t tests were used to compare group means on measures of percent lesion area and IL-6 concentrations. Results There were no group differences in plasma lipids. Adipose tissue samples taken from OT-treated animals secreted significantly less IL-6 over 6 hours (p < .01). OT-treated animals displayed significantly less atherosclerosis in the thoracic aorta (p < .05). Conclusions These results indicate that peripheral OT administration can inhibit atherosclerotic lesion development and adipose tissue inflammation, suggesting a potential role for this neuropeptide in mediating the benefits of stable group housing on atherosclerosis.

Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

“…In addition, chronic systemic OT also reduces the expression of pro-inflammatory markers, such as NF-kB, interleukin 1 beta (IL1-β), and interleukin 6 (IL-6) from heart tissue of db/db mice [93] as well as in rats following myocardial infarction [170]. Interestingly, chronic systemic OT also reduces IL-6 secretion from epididymal fat in hyperlipidemic apolipoprotein E (ApoE) deficient mice [187] and C-reactive protein in Watanabe Heritable Hyperlipidemic rabbits [188]. OTR deficient mice also display increased levels of IL1-β, IL-6 and tumor necrosis factor alpha (TNF-α) mRNA expression in the colons following experimental colitis, findings that suggest a possible protective anti-inflammatory effect [160].…”

Oxytocin: recent developments

“…The reduction in cortisol observed within this study is suggestive of this being due to an anxiolytic effect of oxytocin, but anti-inflammatory and antipain effects are also implicated (122). Additionally, oxytocin can reduce atherosclerosis in ApoE -/-mice, again a result of oxytocins antiinflammatory actions (123).…”

Cardiovascular Action of Oxytocin

“…Oxytocin receptors are expressed in human endothelial cells and THP1 monocyte and macrophage, oxytocin decreased both superoxide production and release of proinflammatory cytokine from these cells [3]. Oxytocin inhibition of inflammatory cytokines has also been demonstrated in both humans and animals in vivo and ex vivo, which may be mediated by stimulation of the cholinergic antiinflammatory pathways [15,16]. It has been shown that oxytocin abolished the sepsis-induced increase in tumor necrosis factor α, and protected against multiple organ damage [17].…”

“…The anti-inflammatory effects of oxytocin are implicated in its regression of atherosclerosis [2,16]. Chronic administration of oxytocin attenuated aortic atherosclerotic lesion development with reduced secretion of the proinflammatory cytokine IL-6 in visceral adipose tissue in social isolated apo-E knockout mice and decreased plasma C-reactive protein level in Watanale Heritble Hyperlipidemic rabbits [12,16]. Clinical and experimental studies have shown that emotion-social stress increases cardiovascular and atherosclerotic diseases [18].…”

“…It has been shown that oxytocin abolished the sepsis-induced increase in tumor necrosis factor α, and protected against multiple organ damage [17]. The anti-inflammatory effects of oxytocin are implicated in its regression of atherosclerosis [2,16]. Chronic administration of oxytocin attenuated aortic atherosclerotic lesion development with reduced secretion of the proinflammatory cytokine IL-6 in visceral adipose tissue in social isolated apo-E knockout mice and decreased plasma C-reactive protein level in Watanale Heritble Hyperlipidemic rabbits [12,16].…”