Chronic Treatment with α-Lipoic Acid Improves Endothelium-Dependent Vasorelaxation of Aortas in High-Fat Diet-Fed Mice

Takenouchi, Yasuhiro; Tsuboi, Kazuhito; Ohsuka, K.; Nobe, Koji; Ohtake, Kazuo; Okamoto, Yasuo; Kasono, Keizo

doi:10.1248/bpb.b18-00800

Cited by 5 publications

(4 citation statements)

References 39 publications

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“…However, endothelial dysfunction in KKAy-Normal mice did not improve following POA administration. Although we have reported on several substances that alter endothelial function in the absence of decreased plasma glucose levels [10,20,29], POA may not improve endothelial function despite its ability to decrease blood glucose levels. On the other hand, POA-induced changes were observed in the aortic contractile response (Figs.…”

Section: Discussionmentioning

confidence: 84%

“…Aortic vascular function was measured as previously described [19][20][21]. Brie y, the thoracic aorta was quickly isolated and immersed in oxygenated, modi ed ice-cold bicarbonate-buffered physiologic salt solution (PSS; containing 137 mM NaCl, 4.73 mM KCl, 1.2 mM MgSO 4 , 0.025 mM EDTA, 1.2 mM KH 2 PO 4 , 2.5 mM CaCl 2 , and 11.1 mM glucose).…”

Section: Measurement Of Isometric Forcementioning

confidence: 99%

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Effects of Dietary Palmitoleic Acid on Vascular Function in Aorta of Diabetic Mice

Takenouchi

Seki

Shiba

et al. 2021

Preprint

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BackgroundChronic 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.MethodsMale KKAy and C57BL/6J mice at the age of 14 weeks were used in the present study. For each mouse strain, one group was fed with normal diet and the other group was fed POA-containing diet for 2 weeks. Then, the vascular reactivities of prepared aortic rings were measured in an organ bath to determine if POA administration changed vascular function in these mice.ResultsKKAy mice treated with POA exhibited decreased plasma glucose levels compared with mice treated with normal 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 control C57BL/6J mice under a normal 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 control mice under a normal diet, but no effect was observed in KKAy mice fed a POA-containing diet. In contrast, there was an increase in vasoconstriction in control mice fed the POA-containing diet compared to mice fed a normal diet. Furthermore, the vasoconstriction in aorta in both control 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.ConclusionThese 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.

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Section: Discussionmentioning

confidence: 84%

Section: Measurement Of Isometric Forcementioning

confidence: 99%

Effects of Dietary Palmitoleic Acid on Vascular Function in Aorta of Diabetic Mice

Takenouchi

Seki

Shiba

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, endothelial dysfunction in KKAy mice did not improve following POA administration. Although we have reported on several substances that alter endothelial function in the absence of decreased plasma glucose levels [ 14 , 28 , 40 ], POA may not improve endothelial function despite its ability to decrease blood glucose levels. On the other hand, POA-induced changes were observed in the aortic contractile response (Figs.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

Self Cite

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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.

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“…Clonidine extended release treatment is effective in children and adolescents with ADHD or Tourette’s disorder [ 175 ]. Analysis of vascular response in normal mice showed that the clonidine-induced relaxation was reduced by inhibiting the PI3K/Akt/eNOS pathway [ 176 ]. Modafinil is an effective drug for the treatment of ADHD [ 177 ].…”

Section: Natural and Synthetic Pi3k Signaling Pathway Modulatorsmentioning

confidence: 99%

Targeting PI3K by Natural Products: A Potential Therapeutic Strategy for Attention-deficit Hyperactivity Disorder

Noori

Sahebgharani

Sureda

et al. 2022

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Attention-Deficit Hyperactivity Disorder (ADHD) is a highly prevalent childhood psychiatric disorder. In general, a child with ADHD has significant attention problems with difficulty concentrating on a subject, and is generally associated with impulsivity and excessive activity. The etiology of ADHD in most patients is unknown, although it is considered to be a multifactorial disease caused by a combination of genetics and environmental factors. Diverse factors such as the existence of mental, nutritional or general health problems during childhood, as well as smoking and alcohol drinking during pregnancy are related to an increased risk of ADHD. Behavioral and psychological characteristics of ADHD include anxiety, mood disorders, behavioral disorders, language disorders, and learning disabilities. These symptoms affect individuals, families, and communities, negatively altering educational and social results, strained parent-child relationships, and increased use of health services. ADHD may be associated with deficits in inhibitory frontostriatal noradrenergic neurons on lower striatal structures that are predominantly driven by dopaminergic neurons. Phosphoinositide 3-kinases (PI3Ks) are a conserved family of lipid kinases that control a number of cellular processes, including cell proliferation, differentiation, migration, insulin metabolism, and apoptosis. Since PI3Ks play an important role in the control of the noradrenergic neuron, it opens up new insights in research on ADHD and other developmental brain diseases. This review presents evidence for potential usefulness of PI3K and its modulators as potential treatment for ADHD.

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Chronic Treatment with α-Lipoic Acid Improves Endothelium-Dependent Vasorelaxation of Aortas in High-Fat Diet-Fed Mice

Cited by 5 publications

References 39 publications

Effects of Dietary Palmitoleic Acid on Vascular Function in Aorta of Diabetic Mice

Effects of Dietary Palmitoleic Acid on Vascular Function in Aorta of Diabetic Mice

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

Targeting PI3K by Natural Products: A Potential Therapeutic Strategy for Attention-deficit Hyperactivity Disorder

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