Effects of dietary palmitoleic acid on vascular function in aorta of diabetic mice

Abstract

Background: Chronic hyperglycemia in diabetes causes atherosclerosis and progresses to diabetic macroangiopathy, and can lead to coronary heart disease, myocardial infarction and cerebrovascular disease. Palmitoleic acid (POA) is a product of endogenous lipogenesis and is present in fish and vegetable oil. In human and animal studies, POA is reported as a beneficial fatty acid related to insulin sensitivity and glucose tolerance. However, few studies have reported its effects on aortic function in diabetes. Here, we investigated the effects of POA administration on vascular function in KKAy mice, a model of type 2 diabetes.

Methods: Male C57BL/6 J (control) and KKAy (experimental) mice at the age of 14 weeks were used in the present study. For each mouse strain, one group was fed with reference diet and a second group was fed POA-containing diet for 2 weeks. The vascular reactivities of prepared aortic rings were then measured in an organ bath to determine if POA administration changed vascular function in these mice.

Results: KKAy mice treated with POA exhibited decreased plasma glucose levels compared with mice treated with reference diet. However, endothelium-dependent vasorelaxant responses to acetylcholine and protease-activated receptor 2 activating protein, which are attenuated in the aorta of KKAy mice compared to C57BL/6 J mice under a reference diet, were not affected by a 2-week POA treatment. In addition, assessment of vasoconstriction revealed that the phenylephrine-induced vasoconstrictive response was enhanced in KKAy mice compared to C57BL/6 J mice under a reference diet, but no effect was observed in KKAy mice fed a POA-containing diet. In contrast, there was an increase in vasoconstriction in C57BL/6 J mice fed the POA-containing diet compared to mice fed a reference diet. Furthermore, the vasoconstriction in aorta in both C57BL/6 J and KKAy mice fed a POA-containing diet were further enhanced under hyperglycemic conditions compared to normal glucose conditions in vitro. In the hyperinsulinemic, and hyperinsulinemic combined with hyperglycemic conditions, vasoconstriction was increased in KKAy mice fed with POA.

Conclusion: These results suggest that POA intake enhances vasoconstriction under hyperglycemic and hyperinsulinemic conditions, which are characteristics of type 2 diabetes, and may contribute to increased vascular complications in diabetes.

Keywords: Diabetes; Palmitoleic acid; Thoracic aorta; Vasoconstriction.

Fig. 1

Body weight (A) and food intake (B) during the experimental period. The horizontal axis represents the number of days since the reference or POA-containing diet was fed to mice. Data are expressed as mean ± S.E.M. A n = 10 for all groups. B n = 3 for C57BL and C57BL-POA, n = 10 for KKAy and KKAy-POA

Fig. 2

Plasma glucose (A) and insulin (B) levels in the four experimental groups. Data are expressed as mean ± S.E.M. of 7-11 mice. *P < 0.05, ***P < 0.001 (one-way ANOVA with Tukey’s multiple comparison test)

Fig. 3

Concentration–response curves following ACh (A), PAR2-AP (B) and SNP (C) treatments of aortic rings. Data are expressed as mean ± S.E.M. of 6 or 7 mice. **P < 0.05, ***P < 0.001 (comparison of the whole concentration-response curves using two-way ANOVA with Tukey multiple comparison test)

Fig. 4

Concentration–response curves following Phe treatment of aortic rings. Data are expressed as mean ± S.E.M. of 4 mice. *P < 0.01, ***P < 0.001 (comparison of the whole concentration-response curves using two-way ANOVA with Tukey multiple comparison test)

Fig. 5

Concentration–response curves following Phe treatment of aortic rings. Organ baths contained normal glucose (NG: 11.1 mM), high glucose (HG: 22.2 mM) or high insulin (HI: 10 μM). Data are expressed as mean ± S.E.M. of 3-4 mice. *P < 0.01, ***P < 0.001 (comparison of the whole concentration-response curves using two-way ANOVA with Tukey multiple comparison test)