Effect of exogenous fatty acids on diabetes neural/neurovascular complications

外源性脂肪酸对糖尿病神经/神经血管并发症的影响

基本信息

  • 批准号:
    9391186
  • 负责人:
  • 金额:
    $ 28.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-12-01 至 2019-11-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Good glycemic control is the only recognized treatment for diabetic peripheral neuropathy (DPN) but studies have shown that it only slows progression. Therefore, other factors besides hyperglycemia must contribute to DPN, and there is a need for a better understanding of what these factors are in order to discover effective treatments. In the proposed studies we will test the hypothesis that different fatty acid classes have either a negative, neutral or positive effect on DPN. Lipids have been shown to be a major risk factor for diseases but there has been no comprehensive analysis of the effect of different classes of fatty acids on DPN. We will use novel rodent models of type 2 diabetes and manipulate diets so as to increase circulating and tissue levels of monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids. Specifically we will examine the potential negative, neutral or positive benefits of dietary enrichment with oleic acid (18:1, MUFA), linoleic acid (18:2, n-6 PUFA), γ-linolenic acid (18:3, n-6 PUFA), α-linolenic acid (18:3, n-3 PUFA) or eicosapentaenoic acid (20:5, EPA, n-3 PUFA) and docosahexaenoic acid (22:6, DHA, n-3 PUFA) on DPN and neurovascular function. The DPN endpoints will include determination of motor and sensory nerve conduction velocity and changes in the density and function of small sensory nerves in the skin and cornea. The latter endpoints will allow us to examine the effect of fatty acid dietary changes on nerve damage or repair. It is expected that supplementing diets of diabetic rodents with oils enriched in oleic acid (olive oil) or linoleic acid (safflower oil) will have little beneicial effect or may even exacerbate DPN and neurovascular dysfunction. Diets supplemented with γ- linolenic acid (evening primrose oil) or α-linolenic acid (flaxseed oil) are expected to be beneficial but to a lesser extent than diets supplemented with EPA and DHA, to be derived from menhaden (fish) oil. We propose that increasing dietary levels of n-3 PUFA (derived from flaxseed oil or menhaden oil) but not γ- linolenic acid (n-6 PUFA derived from evening primrose oil) will lower the n-6 to n-3 fatty acid ratio, a marker for reduced inflammation. Due to reduced ability in diabetes of conversion of α-linolenic acid to EPA we predict that increasing dietary levels of EPA and DHA but not α-linolenic acid will lead to an increased production of resolvins. Resolvins are produced from EPA and DHA by 15-lipoxygenase-1 (15-LOX-1) and have anti-inflammatory and neuroprotective properties. We propose that EPA and DHA treatment of rodents with type 2 diabetes will have the greatest impact on DPN through reducing inflammatory stress, improving neurovascular function and mediating nerve repair. We also propose that treating rodents with salicylsalicylic acid (salsalate) will increase tissue expressio of 15-LOX-1 leading to increased production of resolvins and even greater efficacy toward DPN and neurovascular complications when rodents with type 2 diabetes are treated with the combination of salsalate and menhaden oil. These preclinical studies will provide needed information to justify clinical trials for the treatment of DPN with fish oils and salsalate.


项目成果

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Mark A. Yorek其他文献

Mark A. Yorek的其他文献

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{{ truncateString('Mark A. Yorek', 18)}}的其他基金

Omega-3 Polyunsaturated Fatty Acids in the Treatment of Diabetic Peripheral Neuropathy: Is the source important?
Omega-3 多不饱和脂肪酸治疗糖尿病周围神经病变:来源重要吗?
  • 批准号:
    10447652
  • 财政年份:
    2021
  • 资助金额:
    $ 28.35万
  • 项目类别:
Omega-3 Polyunsaturated Fatty Acids in the Treatment of Diabetic Peripheral Neuropathy: Is the source important?
Omega-3 多不饱和脂肪酸治疗糖尿病周围神经病变:来源重要吗?
  • 批准号:
    10313537
  • 财政年份:
    2021
  • 资助金额:
    $ 28.35万
  • 项目类别:
Omega-3 Polyunsaturated Fatty Acids in the Treatment of Diabetic Peripheral Neuropathy:Is the source important?
Omega-3 多不饱和脂肪酸治疗糖尿病周围神经病变:来源重要吗?
  • 批准号:
    10610377
  • 财政年份:
    2021
  • 资助金额:
    $ 28.35万
  • 项目类别:
Insulin Resistance and Vascular Complications in Obesity and Type 2 Diabetes
肥胖和 2 型糖尿病中的胰岛素抵抗和血管并发症
  • 批准号:
    8327947
  • 财政年份:
    2012
  • 资助金额:
    $ 28.35万
  • 项目类别:
Insulin Resistance and Vascular Complications in Obesity and Type 2 Diabetes
肥胖和 2 型糖尿病中的胰岛素抵抗和血管并发症
  • 批准号:
    8457977
  • 财政年份:
    2012
  • 资助金额:
    $ 28.35万
  • 项目类别:
Insulin Resistance and Vascular Complications in Obesity and Type 2 Diabetes
肥胖和 2 型糖尿病中的胰岛素抵抗和血管并发症
  • 批准号:
    8698322
  • 财政年份:
    2012
  • 资助金额:
    $ 28.35万
  • 项目类别:
Molecular Mechanisms of Age-related Muscle Loss
年龄相关性肌肉损失的分子机制
  • 批准号:
    10368017
  • 财政年份:
    2011
  • 资助金额:
    $ 28.35万
  • 项目类别:
Molecular Mechanisms of Age-related Muscle Loss
年龄相关性肌肉损失的分子机制
  • 批准号:
    10084213
  • 财政年份:
    2011
  • 资助金额:
    $ 28.35万
  • 项目类别:
Peroxynitrite, protein nitration and advanced diabetic neuropathy
过氧亚硝酸盐、蛋白质硝化和晚期糖尿病神经病变
  • 批准号:
    8625363
  • 财政年份:
    2010
  • 资助金额:
    $ 28.35万
  • 项目类别:
Peroxynitrite, protein nitration and advanced diabetic neuropathy
过氧亚硝酸盐、蛋白质硝化和晚期糖尿病神经病变
  • 批准号:
    8664835
  • 财政年份:
    2010
  • 资助金额:
    $ 28.35万
  • 项目类别:

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