Raised saturated-fat intake worsens vascular function in virgin and pregnant offspring of streptozotocin-diabetic rats

Adult offspring of severely diabetic pregnant rats are insulin resistant and display cardiovascular dysfunction. When pregnant they develop mild hyperglycaemia. Diets high in saturated fat have been implicated in the development of cardiovascular disease and vascular dysfunction. In the present study we have determined vascular function in small mesenteric arteries from offspring of normal (OC) and diabetic (OD) rats fed standard chow and offspring of diabetic rats fed a diet high in saturated fats (OD-HF) from weaning to adulthood, and throughout their subsequent pregnancies. OD rats displayed an increased sensitivity to noradrenaline (P < 0·05) and impaired sensitivity to the endothelium-dependent vasodilator, acetylcholine. The component of acetylcholine-induced relaxation attributable to endothelium-derived hyperpolarizing factor was reduced in OD-HF rats. Pregnant OD rats also demonstrated impaired maximum relaxation to acetylcholine (pregnant OD rats v. pregnant OC rats P < 0·05). In pregnant OD-HF rats noradrenaline sensitivity was enhanced and endothelium-dependent relaxation further reduced (pregnant OD-HF rats v. pregnant OC rats P < 0·001). The isoprostane, 8-epi-prostaglandin F2α, a marker of oxidative stress, was increased in pregnant OD rats (pregnant OD rats v. pregnant OC rats P < 0·001) and further increased in pregnant OD-HF rats (pregnant OD-HF rats v. pregnant OD rats P < 0·05). We conclude that a high-saturated-fat diet leads to deterioration in specific components of vascular function in OD rats. When pregnant, vascular function of OD-HF rats is further compromised. Pregnancy in the OD rats is associated with a striking increase in a marker of oxidative stress, which increases further if the saturated fat intake is raised.

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Programming of growth, insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats

Clinical Science ◽

10.1042/cs20080550 ◽

2009 ◽

Vol 117 (3) ◽

pp. 129-138 ◽

Cited By ~ 32

Author(s):

Emily M. Segar ◽

Andrew W. Norris ◽

Jian-Rong Yao ◽

Shanming Hu ◽

Stacia L. Koppenhafer ◽

...

Keyword(s):

Insulin Resistance ◽

Vascular Function ◽

Vascular Dysfunction ◽

Diabetic Rats ◽

Late Gestation ◽

Group Differences ◽

Pregnant Rats ◽

Increased Risk ◽

Specific Insulin ◽

Diabetic Mothers

ODM (offspring of diabetic mothers) have an increased risk of developing metabolic and cardiovascular dysfunction; however, few studies have focused on the susceptibility to disease in offspring of mothers developing diabetes during pregnancy. We developed an animal model of late gestation diabetic pregnancy and characterized metabolic and vascular function in the offspring. Diabetes was induced by streptozotocin (50 mg/kg of body weight, intraperitoneally) in pregnant rats on gestational day 13 and was partially controlled by twice-daily injections of insulin. At 2 months of age, ODM had slightly better glucose tolerance than controls (P<0.05); however, by 6 months of age this trend had reversed. A euglycaemic–hyperinsulinamic clamp revealed insulin resistance in male ODM (P<0.05). In 6–8-month-old female ODM, aortas had significantly enhanced contractility in response to KCl, ET-1 (endothelin-1) and NA (noradrenaline). No differences in responses to ET-1 and NA were apparent with co-administration of L-NNA (NG-nitro-L-arginine). Relaxation in response to ACh (acetylcholine), but not SNP (sodium nitroprusside), was significantly impaired in female ODM. In contrast, males had no between-group differences in response to vasoconstrictors, whereas relaxation to SNP and ACh was greater in ODM compared with control animals. Thus the development of diabetes during pregnancy programmes gender-specific insulin resistance and vascular dysfunction in adult offspring.

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Gender differences in myogenic tone in superoxide dismutase knockout mouse: animal model of oxidative stress

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01179.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. H40-H45 ◽

Cited By ~ 23

Author(s):

Sukrutha Veerareddy ◽

Christy-Lynn M. Cooke ◽

Philip N. Baker ◽

Sandra T. Davidge

Keyword(s):

Oxidative Stress ◽

Vascular Function ◽

Vascular Tone ◽

Vascular Dysfunction ◽

Mesenteric Arteries ◽

Myogenic Tone ◽

Intracellular Enzyme ◽

Male And Female ◽

Prostaglandin H ◽

Myogenic Regulation

Oxidative stress mediated by prooxidants has been implicated in the pathogenesis of vascular disorders. However, the effect of prooxidants on myogenic regulation of vascular function and the differential influence of gender is not known. SOD, an intracellular enzyme, restricts excess prooxidant levels and may limit vascular dysfunction. We therefore tested the effects of Cu,Zn SOD deficiency on vascular tone in both male and female SOD knockout (SOD−/−) mice. We hypothesized that myogenic tone would be enhanced in SOD−/− mice by excess prooxidants compared with wild-type control mice. Indeed, resistance-sized mesenteric arteries from SOD−/− mice exhibited enhanced myogenic tone compared with control mice. Myogenic tone was lower in female than male control mice. Interestingly, this gender effect was absent in SOD−/− mice, such that myogenic tone of mesenteric arteries from females was equated to that of arteries from males. Furthermore, the pathways that modulate myogenic tone were diverse. In both male and female control mice, inhibition of prostaglandin H synthase (PGHS) and nitric oxide synthase (NOS) pathways enhanced myogenic tone. In female SOD−/− mice, inhibition of PGHS and NOS pathways enhanced myogenic tone to a greater extent compared with control mice. Conversely, in male SOD−/− mice, NOS and PGHS inhibition did not alter tone and only inhibition of gap junctions enhanced myogenic tone. In conclusion, this study revealed enhanced myogenic tone in SOD−/− mice compared with control mice. Furthermore, Cu,Zn SOD deficiency particularly enhanced myogenic tone in female mice such that their vascular tone attained the level of male SOD−/− mice, possibly mediated by prooxidants.

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51 MATERNAL SATURATED FAT INTAKE IN PREGNANT RATS PROGRAMMES RENAL AND CARDIOVASCULAR DYSFUNCTION IN HER ADULT OFFSPRING

Journal of Hypertension ◽

10.1097/01.hjh.0000419877.87592.80 ◽

2012 ◽

Vol 30 ◽

pp. e16

Author(s):

Sarah L. Henry ◽

Ryan J. Wood-Bradley ◽

Roger G. Evans ◽

Luise A. Cullen-McEwen ◽

John F. Bertram ◽

...

Keyword(s):

Saturated Fat ◽

Adult Offspring ◽

Fat Intake ◽

Cardiovascular Dysfunction ◽

Pregnant Rats ◽

Saturated Fat Intake

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Faculty Opinions recommendation of Dietary saturated fat intake and atherosclerotic vascular disease mortality in elderly women: a prospective cohort study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725478498.793508191 ◽

2015 ◽

Author(s):

Mikael Fogelholm

Keyword(s):

Cohort Study ◽

Vascular Disease ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Elderly Women ◽

Saturated Fat ◽

Fat Intake ◽

Atherosclerotic Vascular Disease ◽

Disease Mortality ◽

Saturated Fat Intake

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Dietary Fat Intake and Risk of Alzheimer’s Disease and Dementia: A Meta-Analysis of Cohort Studies

Current Alzheimer Research ◽

10.2174/1567205015666180427142350 ◽

2018 ◽

Vol 15 (9) ◽

pp. 869-876 ◽

Cited By ~ 12

Author(s):

Yue Ruan ◽

Jun Tang ◽

Xiaofei Guo ◽

Kelei Li ◽

Duo Li

Keyword(s):

Cohort Studies ◽

Dietary Fat ◽

Prospective Cohort ◽

Meta Analysis ◽

Saturated Fat ◽

Fat Intake ◽

Prospective Cohort Studies ◽

Dietary Fat Intake ◽

Dementia Risk ◽

Saturated Fat Intake

Background: Epidemiological studies showed that dietary fat intake is associated with Alzheimer’s disease (AD) and dementia risk, however, the association remain inconsistent. This metaanalysis aimed to systematically examine the association of dietary fat intake with AD and dementia risk. Methods: We have systematically searched PubMed, Embase and the Cochrane Library up to May 1st 2017. Prospective cohort studies were included if they reported on the association of dietary fat intake with AD and dementia risk. Multivariate-adjusted relative risks (RRs) for the highest versus lowest category were pooled by using a random-effects model. Results: A total of 8630 participants and 633 cases from four independent prospective cohort studies were included in the present meta-analysis. A higher dietary saturated fat intake was significantly associated with an increased risk of 39% and 105% for AD (RR: 1.39; 95% CI: 1.00, 1.94) and dementia (RR: 2.05; 95% CI: 1.06, 3.98), respectively. Dose-response analysis indicated a 4 g/day increment of saturated fat intake was related to 15% higher risk of AD (RR: 1.15; 95% CI: 1.01, 1.31). However, there was no significant association found between dietary intake of total, monounsaturated, polyunsaturated fat and AD or dementia risk. Conclusions: This meta-analysis provides significant evidence of positive association between higher saturated fat intake and AD and dementia risk.

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Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

International Journal of Molecular Sciences ◽

10.3390/ijms22031296 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1296

Author(s):

Yue Ruan ◽

Subao Jiang ◽

Adrian Gericke

Keyword(s):

Oxidative Stress ◽

Macular Degeneration ◽

Vascular Function ◽

Vascular Dysfunction ◽

Therapeutic Strategies ◽

Vision Impairment ◽

Age Related Macular Degeneration ◽

Oxygen Species ◽

Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

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Changes in blood lipid concentrations associated with changes in intake of dietary saturated fat in the context of a healthy low-carbohydrate weight-loss diet: a secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) trial

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy305 ◽

2019 ◽

Vol 109 (2) ◽

pp. 433-441 ◽

Cited By ~ 5

Author(s):

Cynthia W Shih ◽

Michelle E Hauser ◽

Lucia Aronica ◽

Joseph Rigdon ◽

Christopher D Gardner

Keyword(s):

Weight Loss ◽

Lipid Profile ◽

Secondary Analysis ◽

Saturated Fat ◽

Blood Lipid ◽

Carbohydrate Intake ◽

Fat Intake ◽

Weight Loss Diet ◽

Low Carbohydrate ◽

Saturated Fat Intake

ABSTRACTBackgroundFor low-carbohydrate diets, a public health approach has focused on the replacement of carbohydrates with unsaturated fats. However, little research exists on the impacts of saturated fat intake on the lipid profile in the context of whole-food-based low-carbohydrate weight-loss diets.ObjectivesThe primary aim of this secondary analysis of the DIETFITS weight loss trial was to evaluate the associations between changes in percentage of dietary saturated fatty acid intake (%SFA) and changes in low-density lipoproteins, high-density lipoproteins, and triglyceride concentrations for those following a healthy low-carbohydrate (HLC) diet. The secondary aim was to examine these associations specifically for HLC dieters who had the highest 12-month increases in %SFA.MethodsIn the DIETFITS trial, 609 generally healthy adults, aged 18–50 years, with body mass indices of 28–40 kg/m2 were randomly assigned to a healthy low-fat (HLF) or HLC diet for 12 months. In this analysis, linear regression, both without and with adjustment for potential confounders, was used to measure the association between 12-month change in %SFA and blood lipids in 208 HLC participants with complete diet and blood lipid data.ResultsParticipants consumed an average of 12–18% of calories from SFA. An increase of %SFA, without significant changes in absolute saturated fat intake, over 12 months was associated with a statistically significant decrease in triglycerides in the context of a weight-loss study in which participants simultaneously decreased carbohydrate intake. The association between increase in %SFA and decrease in triglycerides was no longer significant when adjusting for 12-month change in carbohydrate intake, suggesting carbohydrate intake may be a mediator of this relationship.ConclusionsThose on a low-carbohydrate weight-loss diet who increase their percentage intake of dietary saturated fat may improve their overall lipid profile provided they focus on a high-quality diet and lower their intakes of both calories and refined carbohydrates. This trial was registered at clinicaltrials.gov as NCT01826591.

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