Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse

Mustad, Vikkie A.; DeMichele, Stephen J.; Huang, Y. S.; Mika, Amanda K.; Lubbers, Nathan L.; Berthiaume, Nathalie; Polakowski, Jim; Zinker, B. A.

doi:10.1016/j.metabol.2006.06.007

Cited by 55 publications

(37 citation statements)

References 35 publications

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“…It is well established that 4 wk of dietary -3 supplementation is sufficient to significantly increase DHA and EPA content of phospholipid pools in virtually all tissues in mice (52)(53)(54)(55)(56)(57)(58)(59). However, despite a relative large percentage increase in DHA and EPA levels, AA levels are only slightly decreased and AA remains as the most abundant tissue PUFA in all reported short-term diet studies in mice (52)(53)(54)(55)(56)(57)(58)(59).…”

Section: Discussionmentioning

confidence: 99%

“…However, despite a relative large percentage increase in DHA and EPA levels, AA levels are only slightly decreased and AA remains as the most abundant tissue PUFA in all reported short-term diet studies in mice (52)(53)(54)(55)(56)(57)(58)(59). A marked increase in eicosanoid production, especially PGE 2 and LXA 4 generation, is induced as a direct consequence of tissue injury and inflammation, due to robust activation of phospholipases and downstream biosynthetic pathways.…”

Section: Discussionmentioning

confidence: 99%

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Acute Changes in Dietary ω-3 and ω-6 Polyunsaturated Fatty Acids Have a Pronounced Impact on Survival following Ischemic Renal Injury and Formation of Renoprotective Docosahexaenoic Acid-Derived Protectin D1

Hassan

Gronert

2009

The Journal of Immunology

102

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Exacerbated inflammation plays an important role in the pathogenesis of ischemic renal injury (IRI), which is the major cause of intrinsic acute renal failure. Clinical studies suggest that long-term treatment with ω-3 polyunsaturated fatty acids (PUFA) improves renal function and lowers the risk of death or end-stage renal disease. Docosahexaenoic acid, a principle ω-3 PUFA of fish oils, is of particular interest as it is found in most human tissues and is converted to protectin D1 (PD1), which exhibits antiinflammatory and proresolving bioactions. We set out to investigate the impact of acute dietary modulation of ω-3 or ω-6 PUFA on IRI and renal lipid autacoid circuits, using an established mouse model and liquid chromatography-mass spectroscopy/mass spectroscopy-based lipidomics. Thirty minutes of renal ischemia significantly elevated serum creatinine in the ω-6 diet group while renal function remained normal in the matched ω-3 diet group. Notably, extending ischemia to 45 min caused 100% mortality in the ω-6 group, in sharp contrast to 0% mortality in the ω-3 group. Protection against IRI in the ω-3 group correlated with decreased polymorphonuclear leukocyte recruitment, chemokine and cytokine levels, abrogated formation of lipoxygenase- and cyclooxygenase-derived eicosanoids, and increased renal levels of PD1. Systemic treatment with PD1 reduced kidney polymorphonuclear leukocyte influx and, more importantly, amplified renoprotective heme-oxygenase-1 protein and mRNA expression in injured and uninjured kidneys. These findings suggest therapeutic or dietary amplification of PD1 circuits restrains acute renal injury and that short-term changes in dietary ω-3 and ω-6 PUFA dramatically impacts renal lipid autacoid formation and outcome of IRI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Acute Changes in Dietary ω-3 and ω-6 Polyunsaturated Fatty Acids Have a Pronounced Impact on Survival following Ischemic Renal Injury and Formation of Renoprotective Docosahexaenoic Acid-Derived Protectin D1

Hassan

Gronert

2009

The Journal of Immunology

102

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“…The ob/ob manifests a pronounced non-insulin dependent diabetes mellitus and obesity observed within 28 days of birth, when compared to their lean littermates [41]. The strain is used as a model for human obesity in a variety of pulmonary, cardiovascular, and metabolic function studies [42][43][44].…”

Section: A Model For the Study Of Obesitymentioning

confidence: 99%

Obesity and vascular dysfunction

et al. 2008

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One of the most profound challenges facing public health and public health policy in Western society is the increased incidence and prevalence of both overweight and obesity. While this condition can have significant consequences for patient mortality and quality of life, it can be further exacerbated as overweight/obesity can be a powerful stimulus for the development of additional risk factors for a negative cardiovascular outcome, including increased insulin resistance, dyslipidemia and hypertension. This manuscript will present the effects of systemic obesity on broad issues of vascular function in both afflicted human populations and in the most relevant animal models. Among the topics that will be covered are alterations to vascular reactivity (both dilator and constrictor responses), adaptations in microvascular network and vessel wall structure, and alterations to the patterns of tissue/organ perfusion as a result of the progression of the obese condition. Additionally, special attention will be paid to the contribution of chronic inflammation as a contributor to alterations in vascular function, as well as the role of perivascular adipose tissue in terms of impacting vessel behavior. When taken together, it is clearly apparent that the development of the obese condition can have profound, and frequently difficult to predict, impacts on integrated vascular function. Much of this complexity appears to have its basis in the extent to which other co-morbidities associated with obesity (e.g., insulin resistance) are present and exert contributing effects.

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“…We also investigated the association with the intermediate-chain length omega-3 PUFA a-linolenic acid (ALA;18:3n-3), an essential fatty acid that is derived from plant sources in the diet and that can also be elongated to longer-chain omega-3 PUFAs in humans. ALA has been found to improve insulin sensitivity in animal models (12), and in some (13,14), but not all (15), shortterm randomized trials, ALA or flaxseed oil, a rich source of ALA, has moderately improved fasting plasma glucose and markers of insulin resistance in humans.…”

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confidence: 99%

Serum Omega-3 Polyunsaturated Fatty Acids and Risk of Incident Type 2 Diabetes in Men: The Kuopio Ischemic Heart Disease Risk Factor Study

et al. 2013

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OBJECTIVEThe relationship between fish or omega-3 polyunsaturated fatty acids (PUFAs) and type 2 diabetes is inconclusive. Even contaminants in fish, such as mercury, may modify the effects. We investigated the associations between serum omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), a-linolenic acid (ALA), hair mercury, and risk of incident type 2 diabetes in middle-aged and older Finnish men. RESEARCH DESIGN AND METHODSA total of 2,212 men from the prospective, population-based Kuopio Ischemic Heart Disease Risk Factor study, aged 42-60 years and free of type 2 diabetes at baseline in 1984-1989, were investigated. Serum PUFA and hair mercury were used as biomarkers for exposure. Dietary intakes were assessed with 4-day food recording. Type 2 diabetes was assessed by self-administered questionnaires and fasting and 2-h oral glucose tolerance test blood glucose measurement at reexamination rounds 4, 11, and 20 years after the baseline and by record linkage to hospital discharge registry and reimbursement register on diabetes medication expenses. Cox proportional hazards models were used to analyze associations. RESULTSDuring the average follow-up of 19.3 years, 422 men developed type 2 diabetes. Men in the highest versus the lowest serum EPA + DPA + DHA quartile had 33% lower multivariate-adjusted risk for type 2 diabetes (95% CI 13-49; P trend 0.01). No statistically significant associations were observed with serum or dietary ALA, dietary fish or EPA + DHA, or hair mercury. CONCLUSIONSSerum long-chain omega-3 PUFA concentration, an objective biomarker for fish intake, was associated with long-term lower risk of type 2 diabetes.

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Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse

Cited by 55 publications

References 35 publications

Acute Changes in Dietary ω-3 and ω-6 Polyunsaturated Fatty Acids Have a Pronounced Impact on Survival following Ischemic Renal Injury and Formation of Renoprotective Docosahexaenoic Acid-Derived Protectin D1

Acute Changes in Dietary ω-3 and ω-6 Polyunsaturated Fatty Acids Have a Pronounced Impact on Survival following Ischemic Renal Injury and Formation of Renoprotective Docosahexaenoic Acid-Derived Protectin D1

Obesity and vascular dysfunction

Serum Omega-3 Polyunsaturated Fatty Acids and Risk of Incident Type 2 Diabetes in Men: The Kuopio Ischemic Heart Disease Risk Factor Study

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