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Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. Due to its high prevalence, and its link to hepatocellular carcinoma (HCC), studying the pathogenesis of NAFLD is crucial. Unconventional prefoldin RPB5 interactor 1 (URI1) belongs to the prefoldin family of proteins that have been shown to coordinate nutrient availability by transcriptional regulation of genes involved in glucose and lipid metabolism. URI1 has been shown to be elevated in mouse liver after induction of NAFLD by a high fat diet and contributes to the development of HCC. Trans-10, cis-12 conjugated linoleic acid (t10,c12 CLA) is marketed as a weight loss supplement and feeding t10,c12 CLA to mice results in hepatic steatosis (the earliest stage of NAFLD characterized by hepatic lipid accumulation). In this thesis, it is hypothesized that t10,c12 CLA feeding of lean and obese db/db mice facilitates hepatic steatosis through upregulation of URI1 protein expression. The validity of this hypothesis was assessed using in vivo (mouse) and in vitro (H4IIE cell line) experimental models, which included heterozygous and homozygous Uri1 knock out (KO) H4IIE cell lines, which were generated using the CRISPR/Cas9 system. T10,c12 CLA feeding promoted hepatic steatosis in both lean and db/db mice, compared to mice fed the control diet, by upregulating hepatic de novo lipogenesis and fatty acid uptake which, potentially, may occur by t10,c12 CLA-mediated activation of the mammalian target of rapamycin pathway. Obesity- and t10,c12 CLA-induced hepatic steatosis also resulted in i increased hepatic URI1 levels. In parallel, URI1 protein levels and neutral lipid accumulation in vitro were both elevated the most after 24 hours of oleic acid (OA) treatment. Lastly, in comparison to wild type H4IIE cells, Uri1 KO H4IIE cells exhibited fewer lipid droplets in response to OA treatment, suggesting a role for URI1 in hepatic lipid accumulation. In conclusion, t10,c12 CLA may promote

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. Due to its high prevalence, and its link to hepatocellular carcinoma (HCC), studying the pathogenesis of NAFLD is crucial. Unconventional prefoldin RPB5 interactor 1 (URI1) belongs to the prefoldin family of proteins that have been shown to coordinate nutrient availability by transcriptional regulation of genes involved in glucose and lipid metabolism. URI1 has been shown to be elevated in mouse liver after induction of NAFLD by a high fat diet and contributes to the development of HCC. Trans-10, cis-12 conjugated linoleic acid (t10,c12 CLA) is marketed as a weight loss supplement and feeding t10,c12 CLA to mice results in hepatic steatosis (the earliest stage of NAFLD characterized by hepatic lipid accumulation). In this thesis, it is hypothesized that t10,c12 CLA feeding of lean and obese db/db mice facilitates hepatic steatosis through upregulation of URI1 protein expression. The validity of this hypothesis was assessed using in vivo (mouse) and in vitro (H4IIE cell line) experimental models, which included heterozygous and homozygous Uri1 knock out (KO) H4IIE cell lines, which were generated using the CRISPR/Cas9 system. T10,c12 CLA feeding promoted hepatic steatosis in both lean and db/db mice, compared to mice fed the control diet, by upregulating hepatic de novo lipogenesis and fatty acid uptake which, potentially, may occur by t10,c12 CLA-mediated activation of the mammalian target of rapamycin pathway. Obesity- and t10,c12 CLA-induced hepatic steatosis also resulted in i increased hepatic URI1 levels. In parallel, URI1 protein levels and neutral lipid accumulation in vitro were both elevated the most after 24 hours of oleic acid (OA) treatment. Lastly, in comparison to wild type H4IIE cells, Uri1 KO H4IIE cells exhibited fewer lipid droplets in response to OA treatment, suggesting a role for URI1 in hepatic lipid accumulation. In conclusion, t10,c12 CLA may promote

Consuming pulses over several weeks improves vascular function and decreases cardiovascular disease risk; however, it is unknown whether pulses can positively modulate postprandial vascular responses, a delimiting factor in projecting vascular health. Bioactive compounds within pulses are the suggested effectors; thus, dry beans (Phaseolus vulgaris L.) were investigated due to their contrasting seed coat colours, indicative of distinct phytochemical profiles. A randomized crossover study investigated the effects of beans with different seed coat colours (white, tan, red, and black) on postprandial vascular and metabolic responses in healthy adults. Darker-coloured beans induced positive postprandial vascular responses, as evidenced by blood vessel relaxation within six hours of consumption. Additionally, the different beans elicited distinct responses for various vascular and metabolic parameters depending on seed coat colour. Thus, bioactive compounds unique to each bean type are likely responsible for the different biological effects. To investigate potential vasorelaxation mechanisms, serum samples were analyzed by untargetted metabolomics to identify novel endogenous metabolites that changed following consumption of the different bean types. Darker-coloured beans altered 47 metabolites within six hours that were unchanged by lighter-coloured beans. Circulating acylcarnitines were tentatively identified as compounds of interest because they are linked to improved blood flow, but absolute identities were not confirmed. The chronic effects of navy and black beans on vascular structure and function were investigated in spontaneously hypertensive rats, a model of essential hypertension. Black beans, but not navy beans, improved vascular compliance of mesenteric resistance arteries, but this was reversed when bean consumption ceased for 4 weeks. These findings indicate that regular consumption of black beans was required to retain the positive effects on the vasculatu

Consuming pulses over several weeks improves vascular function and decreases cardiovascular disease risk; however, it is unknown whether pulses can positively modulate postprandial vascular responses, a delimiting factor in projecting vascular health. Bioactive compounds within pulses are the suggested effectors; thus, dry beans (Phaseolus vulgaris L.) were investigated due to their contrasting seed coat colours, indicative of distinct phytochemical profiles. A randomized crossover study investigated the effects of beans with different seed coat colours (white, tan, red, and black) on postprandial vascular and metabolic responses in healthy adults. Darker-coloured beans induced positive postprandial vascular responses, as evidenced by blood vessel relaxation within six hours of consumption. Additionally, the different beans elicited distinct responses for various vascular and metabolic parameters depending on seed coat colour. Thus, bioactive compounds unique to each bean type are likely responsible for the different biological effects. To investigate potential vasorelaxation mechanisms, serum samples were analyzed by untargetted metabolomics to identify novel endogenous metabolites that changed following consumption of the different bean types. Darker-coloured beans altered 47 metabolites within six hours that were unchanged by lighter-coloured beans. Circulating acylcarnitines were tentatively identified as compounds of interest because they are linked to improved blood flow, but absolute identities were not confirmed. The chronic effects of navy and black beans on vascular structure and function were investigated in spontaneously hypertensive rats, a model of essential hypertension. Black beans, but not navy beans, improved vascular compliance of mesenteric resistance arteries, but this was reversed when bean consumption ceased for 4 weeks. These findings indicate that regular consumption of black beans was required to retain the positive effects on the vasculatu

Xenin is a gastrointestinal hormone reported to supress food intake. Little is known about the role of xenin in body weight regulation. I hypothesized that enhanced xenin action will cause alterations in lipid metabolism towards reducing adiposity and body weight. To address this hypothesis, the present study investigated the effect of intracerebroventricular (i.c.v.) xenin treatment on body weight and lipid metabolism in obese mice. Effects of xenin on lipid metabolism were also investigated ex vivo in cultured gonadal white adipose tissue (WAT) and 3T3-L1 adipocytes. I.c.v. xenin treatment reduced body weight gain and increased phosphorylation of hormone sensitive lipase (HSL) in WAT of obese mice. Xenin treatment increased glycerol, free fatty acid (FFA) release and phosphorylation of HSL ex vivo in cultured WAT and 3T3-L1 adipocytes. These findings suggest that enhanced xenin action may be beneficial in reversing obesity by increasing the use of stored fats for fuel.

Pulses such as dried beans may be useful in the treatment of hypertension. Vascular protection by beans may relate to their phenolic compounds, which are associated with darker-coloured seeds. Thus, black beans were compared to navy beans for their effects on hypertension and vascular remodelling in spontaneously hypertensive rats (SHR). Assessments of blood pressure, pulse wave velocity (PWV), and vessel morphology were conducted to ascertain the vascular effects of the beans. Results showed that neither black beans nor navy beans influenced blood pressure or PWV in SHR. However, vascular remodelling was mitigated by black beans but not by navy beans. This was indicated by the absence of a significant difference in the ratio of aortic elastin content to vessel wall area in black bean-fed SHR compared to normotensive Wistar Kyoto (WKY) rats. The consumption of black beans could therefore be a therapeutic dietary strategy for combating vascular remodelling in hypertension.

Xenin is a gastrointestinal hormone reported to supress food intake. Little is known about the role of xenin in body weight regulation. I hypothesized that enhanced xenin action will cause alterations in lipid metabolism towards reducing adiposity and body weight. To address this hypothesis, the present study investigated the effect of intracerebroventricular (i.c.v.) xenin treatment on body weight and lipid metabolism in obese mice. Effects of xenin on lipid metabolism were also investigated ex vivo in cultured gonadal white adipose tissue (WAT) and 3T3-L1 adipocytes. I.c.v. xenin treatment reduced body weight gain and increased phosphorylation of hormone sensitive lipase (HSL) in WAT of obese mice. Xenin treatment increased glycerol, free fatty acid (FFA) release and phosphorylation of HSL ex vivo in cultured WAT and 3T3-L1 adipocytes. These findings suggest that enhanced xenin action may be beneficial in reversing obesity by increasing the use of stored fats for fuel.

Pulses such as dried beans may be useful in the treatment of hypertension. Vascular protection by beans may relate to their phenolic compounds, which are associated with darker-coloured seeds. Thus, black beans were compared to navy beans for their effects on hypertension and vascular remodelling in spontaneously hypertensive rats (SHR). Assessments of blood pressure, pulse wave velocity (PWV), and vessel morphology were conducted to ascertain the vascular effects of the beans. Results showed that neither black beans nor navy beans influenced blood pressure or PWV in SHR. However, vascular remodelling was mitigated by black beans but not by navy beans. This was indicated by the absence of a significant difference in the ratio of aortic elastin content to vessel wall area in black bean-fed SHR compared to normotensive Wistar Kyoto (WKY) rats. The consumption of black beans could therefore be a therapeutic dietary strategy for combating vascular remodelling in hypertension.

Non-targeted liquid chromatography-mass spectrometry (LC-MS) based metabolomics methods were used to determine whether bean consumption affects the profile of metabolites in serum and urine of individuals with peripheral artery disease. Urine and serum collected at baseline or after 8 weeks of consuming 1.5 or 3 cups per week of cooked mixed beans (pinto, red kidney, black and navy) or pulse-free foods, was extracted with acetonitrile and analyzed by non-targeted LC-QTOF-MS methods. Several compounds found in beans were present in the biological fluids indicating that these compounds may be useful markers of bean consumption. Bean consumption significantly (P<0.05) altered several endogenous metabolites including amino acids, glutathione, bile salts, phospholipids and products of arachidonic acid metabolism by cyclooxygenase. The decrease in the metabolites of an anti-hypertensive drug in urine after 8 weeks of bean consumption suggested the existence of potential drug-diet interactions that could affect the required dosage of certain anti-hypertensive medications.

Adiponectin is an abundant hormone secreted by adipocytes that exhibits anti-diabetic, anti-inflammatory and anti-atherogenic properties. However, in obesity, as adipocytes enlarge, adiponectin secretion declines. A sex dimorphism is observed in adiponectin levels with women having higher levels than men. We hypothesized that a lack of adiponectin negatively affects both insulin sensitivity and adipose physiology in a sex-dependent manner. In this study, male and female adiponectin knockout or wild-type mice were fed with either a low fat or high fat diet. Male knockout animals were more glucose intolerant and had elevated fasting glucose levels. In contrast, both adiponectin knockout and wild-type females showed decreased hepatic lipid accumulation on a high fat diet. In both sexes, lean adiponectin knockout mice had significantly smaller fat depot weights and lesser hepatic lipid accumulation than the lean wild-type mice. However, on high fat diet, only male adiponectin knockout mice had fat depot weights that were comparable to wild-type mice, which indicate a novel sex-specific role of adiponectin in determining adiposity.

The endocannabinoid (EC) system has a role in metabolic homeostasis. The purpose of this study was to determine the effect of ECs and the fatty acids they are derived from on lipid metabolism and mitochondrial function in adipocytes. 3T3-L1 adipocytes on day 8 of differentiation were treated with ECs and fatty acids for 48 hours in the absence or presence of insulin and various inhibitors. Lysates were analyzed via Western immunoblotting, a lipolysis assay and Seahorse XF Analyzer for changes in protein levels, phosphorylation state, lipolysis, and oxygen consumption rate. Results showed that ECs (2-arachidonoyl glycerol) stimulated lipolysis via a novel AMPK-dependent pathway, while fatty acids had varying effects on insulin signaling and mitochondrial function . These data suggest adipose tissue EC receptors may be a suitable target for anti-obesity therapy. Further research is needed to understand how the dietary fatty acid profile may influence synthesis of ECs.

Non-targeted liquid chromatography-mass spectrometry (LC-MS) based metabolomics methods were used to determine whether bean consumption affects the profile of metabolites in serum and urine of individuals with peripheral artery disease. Urine and serum collected at baseline or after 8 weeks of consuming 1.5 or 3 cups per week of cooked mixed beans (pinto, red kidney, black and navy) or pulse-free foods, was extracted with acetonitrile and analyzed by non-targeted LC-QTOF-MS methods. Several compounds found in beans were present in the biological fluids indicating that these compounds may be useful markers of bean consumption. Bean consumption significantly (P<0.05) altered several endogenous metabolites including amino acids, glutathione, bile salts, phospholipids and products of arachidonic acid metabolism by cyclooxygenase. The decrease in the metabolites of an anti-hypertensive drug in urine after 8 weeks of bean consumption suggested the existence of potential drug-diet interactions that could affect the required dosage of certain anti-hypertensive medications.

Adiponectin is an abundant hormone secreted by adipocytes that exhibits anti-diabetic, anti-inflammatory and anti-atherogenic properties. However, in obesity, as adipocytes enlarge, adiponectin secretion declines. A sex dimorphism is observed in adiponectin levels with women having higher levels than men. We hypothesized that a lack of adiponectin negatively affects both insulin sensitivity and adipose physiology in a sex-dependent manner. In this study, male and female adiponectin knockout or wild-type mice were fed with either a low fat or high fat diet. Male knockout animals were more glucose intolerant and had elevated fasting glucose levels. In contrast, both adiponectin knockout and wild-type females showed decreased hepatic lipid accumulation on a high fat diet. In both sexes, lean adiponectin knockout mice had significantly smaller fat depot weights and lesser hepatic lipid accumulation than the lean wild-type mice. However, on high fat diet, only male adiponectin knockout mice had fat depot weights that were comparable to wild-type mice, which indicate a novel sex-specific role of adiponectin in determining adiposity.

The endocannabinoid (EC) system has a role in metabolic homeostasis. The purpose of this study was to determine the effect of ECs and the fatty acids they are derived from on lipid metabolism and mitochondrial function in adipocytes. 3T3-L1 adipocytes on day 8 of differentiation were treated with ECs and fatty acids for 48 hours in the absence or presence of insulin and various inhibitors. Lysates were analyzed via Western immunoblotting, a lipolysis assay and Seahorse XF Analyzer for changes in protein levels, phosphorylation state, lipolysis, and oxygen consumption rate. Results showed that ECs (2-arachidonoyl glycerol) stimulated lipolysis via a novel AMPK-dependent pathway, while fatty acids had varying effects on insulin signaling and mitochondrial function . These data suggest adipose tissue EC receptors may be a suitable target for anti-obesity therapy. Further research is needed to understand how the dietary fatty acid profile may influence synthesis of ECs.

Time course changes in oxylipin profiles among healthy, young individuals consuming high doses of alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) remain to be determined. Differences in lipid metabolism suggest the importance of separating sexes when investigating the effect of omega-3 supplementation on the oxylipin profile. Individuals (n=12) participated in a double-blind randomized cross-over trial where ALA oil (4g/day ALA) and DHA oil (4g/day DHA) were consumed for four weeks. Oxylipins from plasma, serum, and supplemental oils were analyzed. Females responded more immediately than males to DHA oil treatment and had higher levels of several DHA derived oxylipins, while ALA oil had a minimal effect on oxylipin production. Several oxylipins were elevated in serum when compared to plasma. Further, oxylipins were present in both supplemental oils. These results can be used to further explore oxylipin profiles in males and females and to help explain the impact of omega-3 supplementation.

Time course changes in oxylipin profiles among healthy, young individuals consuming high doses of alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) remain to be determined. Differences in lipid metabolism suggest the importance of separating sexes when investigating the effect of omega-3 supplementation on the oxylipin profile. Individuals (n=12) participated in a double-blind randomized cross-over trial where ALA oil (4g/day ALA) and DHA oil (4g/day DHA) were consumed for four weeks. Oxylipins from plasma, serum, and supplemental oils were analyzed. Females responded more immediately than males to DHA oil treatment and had higher levels of several DHA derived oxylipins, while ALA oil had a minimal effect on oxylipin production. Several oxylipins were elevated in serum when compared to plasma. Further, oxylipins were present in both supplemental oils. These results can be used to further explore oxylipin profiles in males and females and to help explain the impact of omega-3 supplementation.

Jennifer E Enns,1,2 Peter Zahradka,1–3 Randolph P Guzman,4,5 Alanna Baldwin,1 Brendon Foot,1 Carla G Taylor1–31Canadian Centre for Agri-Food Research in Health and Medicine, St Boniface Research Centre, Winnipeg, Canada; 2Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada; 3Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; 4IH Asper Clinical Research Institute, St Boniface Hospital, Winnipeg, Canada; 5Section of Vascular Surgery, Department of Surgery, St Boniface Hospital, Winnipeg, CanadaBackground: Individuals with peripheral arterial disease (PAD) are at high risk for cardiac events due to atherosclerosis. Dietary fatty acid composition has been shown to modulate blood vessel properties, but whether a diet enriched in conventional canola oil can improve clinical endpoints in PAD is not known.Purpose: To describe the rationale and design of a clinical trial testing the effect of canola oil consumption on vascular function and cardiovascular risk factors in an 8-week dietary intervention in individuals with PAD.Methods: The Canola-PAD Study was a single center, prospective, double-blind, randomized controlled trial in 50 patients over 40 years old with PAD. Participants were randomized into two groups and consumed food items containing either conventional canola oil (25 g/day) or an oil mixture representing the Western diet (25 g/day) for 8 weeks as part of their usual diet. The primary outcome was vascular function (ankle-brachial index, arterial stiffness, endothelial dysfunction, walking capacity, and cognitive function). Secondary measurements included anthropometrics, serum lipid profile and fatty acid composition, markers of inflammation and glycemic control, and serum metabolite profile.Discussion: The Canola-PAD Study uses an innovative and noninvasive approach to evaluate the effect of canola oil on clinically relevant outcomes in individuals with PAD, including arte

Consumption of pulse crops has been linked to improvements in blood vessel function, but which pulse variety/type is better and how they work remains unknown. Two distinct studies were conducted to address these questions. In study 1, spontaneously hypertensive rats (SHR) were fed control diet, or diets containing 30% (w/w) beans, peas, lentils, chickpeas, or mixed pulses. Normotensive Wistar-Kyoto (WKY) rats were fed the control diet. The lentil–containing diet significantly attenuated the rise in BP (+8 and +31 mmHg, vs. control) and reduced large artery remodeling compared to control. In study 2, SHR were fed control, mixed lentil, green lentil, or red lentil diets for 8 weeks. WKY were fed control or mixed lentil diets. Green lentils decreased arterial remodeling and improved arterial compliance in the SHR. A diet high in green lentils could be a valuable adjunct to allopathic medicine to mitigate effects of hypertension on the vasculature.

Peripheral artery disease (PAD) is one of the most common cardiovascular diseases. Despite high prevalence of PAD, data regarding the dietary patterns of Canadian individuals with PAD is required. Biomarkers are used as an alternative to dietary assessment methods and are generally used to measure true dietary intake. A total of 30 participants with established PAD were recruited for this study. Dietary intakes were estimated using a 3 day food record (3DFR) and food frequency questionnaire (FFQ). Docosahexaenoic acid (DHA) status was analyzed in plasma, plasma PL and RBC membrane PL. The determined mean dietary macronutrient distribution consisted of 18% protein, 33% fat and 47% carbohydrate with 3DFR and 19% protein, 36% fat and 43% carbohydrate with FFQ. The mean intakes using 3DFR and FFQ, respectively, were: saturated fat = 24.2, 22.8 g; sodium = 4156.6, 2852.3 mg; eicosapentaenoic acid (EPA) = 90.0, 50.0 mg and DHA = 128.5, 110.0 mg. FFQ showed significant (p<0.05) correlation (r=0.48) with plasma and plasma PL DHA. As compared to national guidelines, the participants consumed a diet that was 61% higher than National Cholesterol Education Program (NCEP) recommendations for saturated fat. Also, the participants consumed a diet which was 177% and 246% higher than NCEP and the Institute of Medicine (IOM) recommendations for sodium, respectively. Hence, PAD patients should be encouraged to eat a diet that is lower in saturated fat and sodium. None of the participants met the American Heart Association (AHA) recommendations for established cardiovascular disease of 1g of combined EPA and DHA.

Basic and clinical research documents the benefits of dietary milled flaxseed (MFX), a rich source of alpha-linolenic acid (ALA) and lignans, in the attenuation of risk factors key to regulating cardiovascular disease (CVD) progression. ALA has antihypertensive properties and the lignan metabolites, enterodiol (END) and enterolactone (ENL), have antioxidative potential. The effectiveness of these bioactives to reduce risk factors of CVD may be dependent upon their plasma concentrations. To study this, we first designed and validated a method using supported liquid extraction and gas chromatography/mass spectrometry to isolate and quantify enterolignans in plasma. Applying this technique, we examined MFX doses of 10-40 g/d administered to healthy, younger adults (18-49 years of age) for 4 weeks. Ten g/d was sufficient to significantly increase circulating ALA (1.5 fold) and enterolignans (5-31 fold). There was no significant dose-dependent response. In another investigation, younger (18-29 years of age) and older (45-69 years of age) healthy adults were studied to determine if age influenced enterolignan metabolism. CVD is associated with advanced age but older people may not be able to obtain lignan metabolites from dietary MFX. Following 4 weeks of MFX consumption, both age groups increased plasma total enterolignans (END + ENL) with no between-group differences. This suggested that older and younger adults metabolize MFX lignans equally. A final study assessed MFX bioactives in plasma of peripheral artery disease patients >40 years of age. Plasma enterolignans increased 10-50 fold and ALA 1-2 fold after only one month of MFX ingestion. Dietary MFX also attenuated total (11%) and LDL (15%) cholesterol in these patients after 1-6 months of administered MFX compared to placebo. The attenuation in cholesterol was due to the high fiber content of flaxseed, and not to ALA and enterolignans, despite their marked increase in circulation. MFX did not interfere with cholest

Basic and clinical research documents the benefits of dietary milled flaxseed (MFX), a rich source of alpha-linolenic acid (ALA) and lignans, in the attenuation of risk factors key to regulating cardiovascular disease (CVD) progression. ALA has antihypertensive properties and the lignan metabolites, enterodiol (END) and enterolactone (ENL), have antioxidative potential. The effectiveness of these bioactives to reduce risk factors of CVD may be dependent upon their plasma concentrations. To study this, we first designed and validated a method using supported liquid extraction and gas chromatography/mass spectrometry to isolate and quantify enterolignans in plasma. Applying this technique, we examined MFX doses of 10-40 g/d administered to healthy, younger adults (18-49 years of age) for 4 weeks. Ten g/d was sufficient to significantly increase circulating ALA (1.5 fold) and enterolignans (5-31 fold). There was no significant dose-dependent response. In another investigation, younger (18-29 years of age) and older (45-69 years of age) healthy adults were studied to determine if age influenced enterolignan metabolism. CVD is associated with advanced age but older people may not be able to obtain lignan metabolites from dietary MFX. Following 4 weeks of MFX consumption, both age groups increased plasma total enterolignans (END + ENL) with no between-group differences. This suggested that older and younger adults metabolize MFX lignans equally. A final study assessed MFX bioactives in plasma of peripheral artery disease patients >40 years of age. Plasma enterolignans increased 10-50 fold and ALA 1-2 fold after only one month of MFX ingestion. Dietary MFX also attenuated total (11%) and LDL (15%) cholesterol in these patients after 1-6 months of administered MFX compared to placebo. The attenuation in cholesterol was due to the high fiber content of flaxseed, and not to ALA and enterolignans, despite their marked increase in circulation. MFX did not interfere with cholest

Consumption of pulse crops has been linked to improvements in blood vessel function, but which pulse variety/type is better and how they work remains unknown. Two distinct studies were conducted to address these questions. In study 1, spontaneously hypertensive rats (SHR) were fed control diet, or diets containing 30% (w/w) beans, peas, lentils, chickpeas, or mixed pulses. Normotensive Wistar-Kyoto (WKY) rats were fed the control diet. The lentil–containing diet significantly attenuated the rise in BP (+8 and +31 mmHg, vs. control) and reduced large artery remodeling compared to control. In study 2, SHR were fed control, mixed lentil, green lentil, or red lentil diets for 8 weeks. WKY were fed control or mixed lentil diets. Green lentils decreased arterial remodeling and improved arterial compliance in the SHR. A diet high in green lentils could be a valuable adjunct to allopathic medicine to mitigate effects of hypertension on the vasculature.

Peripheral artery disease (PAD) is one of the most common cardiovascular diseases. Despite high prevalence of PAD, data regarding the dietary patterns of Canadian individuals with PAD is required. Biomarkers are used as an alternative to dietary assessment methods and are generally used to measure true dietary intake. A total of 30 participants with established PAD were recruited for this study. Dietary intakes were estimated using a 3 day food record (3DFR) and food frequency questionnaire (FFQ). Docosahexaenoic acid (DHA) status was analyzed in plasma, plasma PL and RBC membrane PL. The determined mean dietary macronutrient distribution consisted of 18% protein, 33% fat and 47% carbohydrate with 3DFR and 19% protein, 36% fat and 43% carbohydrate with FFQ. The mean intakes using 3DFR and FFQ, respectively, were: saturated fat = 24.2, 22.8 g; sodium = 4156.6, 2852.3 mg; eicosapentaenoic acid (EPA) = 90.0, 50.0 mg and DHA = 128.5, 110.0 mg. FFQ showed significant (p<0.05) correlation (r=0.48) with plasma and plasma PL DHA. As compared to national guidelines, the participants consumed a diet that was 61% higher than National Cholesterol Education Program (NCEP) recommendations for saturated fat. Also, the participants consumed a diet which was 177% and 246% higher than NCEP and the Institute of Medicine (IOM) recommendations for sodium, respectively. Hence, PAD patients should be encouraged to eat a diet that is lower in saturated fat and sodium. None of the participants met the American Heart Association (AHA) recommendations for established cardiovascular disease of 1g of combined EPA and DHA.

Basic and clinical research documents the benefits of dietary milled flaxseed (MFX), a rich source of alpha-linolenic acid (ALA) and lignans, in the attenuation of risk factors key to regulating cardiovascular disease (CVD) progression. ALA has antihypertensive properties and the lignan metabolites, enterodiol (END) and enterolactone (ENL), have antioxidative potential. The effectiveness of these bioactives to reduce risk factors of CVD may be dependent upon their plasma concentrations. To study this, we first designed and validated a method using supported liquid extraction and gas chromatography/mass spectrometry to isolate and quantify enterolignans in plasma. Applying this technique, we examined MFX doses of 10-40 g/d administered to healthy, younger adults (18-49 years of age) for 4 weeks. Ten g/d was sufficient to significantly increase circulating ALA (1.5 fold) and enterolignans (5-31 fold). There was no significant dose-dependent response. In another investigation, younger (18-29 years of age) and older (45-69 years of age) healthy adults were studied to determine if age influenced enterolignan metabolism. CVD is associated with advanced age but older people may not be able to obtain lignan metabolites from dietary MFX. Following 4 weeks of MFX consumption, both age groups increased plasma total enterolignans (END + ENL) with no between-group differences. This suggested that older and younger adults metabolize MFX lignans equally. A final study assessed MFX bioactives in plasma of peripheral artery disease patients >40 years of age. Plasma enterolignans increased 10-50 fold and ALA 1-2 fold after only one month of MFX ingestion. Dietary MFX also attenuated total (11%) and LDL (15%) cholesterol in these patients after 1-6 months of administered MFX compared to placebo. The attenuation in cholesterol was due to the high fiber content of flaxseed, and not to ALA and enterolignans, despite their marked increase in circulation. MFX did not interfere with cholest

Basic and clinical research documents the benefits of dietary milled flaxseed (MFX), a rich source of alpha-linolenic acid (ALA) and lignans, in the attenuation of risk factors key to regulating cardiovascular disease (CVD) progression. ALA has antihypertensive properties and the lignan metabolites, enterodiol (END) and enterolactone (ENL), have antioxidative potential. The effectiveness of these bioactives to reduce risk factors of CVD may be dependent upon their plasma concentrations. To study this, we first designed and validated a method using supported liquid extraction and gas chromatography/mass spectrometry to isolate and quantify enterolignans in plasma. Applying this technique, we examined MFX doses of 10-40 g/d administered to healthy, younger adults (18-49 years of age) for 4 weeks. Ten g/d was sufficient to significantly increase circulating ALA (1.5 fold) and enterolignans (5-31 fold). There was no significant dose-dependent response. In another investigation, younger (18-29 years of age) and older (45-69 years of age) healthy adults were studied to determine if age influenced enterolignan metabolism. CVD is associated with advanced age but older people may not be able to obtain lignan metabolites from dietary MFX. Following 4 weeks of MFX consumption, both age groups increased plasma total enterolignans (END + ENL) with no between-group differences. This suggested that older and younger adults metabolize MFX lignans equally. A final study assessed MFX bioactives in plasma of peripheral artery disease patients >40 years of age. Plasma enterolignans increased 10-50 fold and ALA 1-2 fold after only one month of MFX ingestion. Dietary MFX also attenuated total (11%) and LDL (15%) cholesterol in these patients after 1-6 months of administered MFX compared to placebo. The attenuation in cholesterol was due to the high fiber content of flaxseed, and not to ALA and enterolignans, despite their marked increase in circulation. MFX did not interfere with cholest

Dietary fat has long been implicated in the etiology of metabolic and cardiovascular disease, and both the amount of fat and the fatty acid composition of the diet play a role in disease progression. Although national health organizations have set guidelines for the recommended intake of dietary fats, questions remain regarding the optimal dietary lipid profile for maintaining health and improving disease conditions. Whether certain types of fatty acids from plant-based oils can improve metabolic and vascular disease has been studied and debated, but not fully determined. In this study, we investigated the role of dietary fatty acids from plant-based oils, and examined their effects on metabolic and vascular disease parameters. Obese fa/fa Zucker rats were fed a diet containing flaxseed oil, which resulted in smaller adipocytes and decreased adipose tissue T-cell infiltration. Obese-prone Sprague Dawley rats were fed high-fat diets with different proportions of mono- and polyunsaturated fats. Changes were observed in adipose tissue levels of fatty acid synthase, adiponectin and fatty acid receptors GPR41 and GPR43, but other metabolic and inflammatory mediators in adipose tissue and serum remained stable. A systematic review and meta-analysis on the impact of n3 fatty acids on major cardiovascular endpoints showed that little evidence exists to support their role in peripheral arterial disease. Then again, very few studies on this topic have been conducted. To address this research gap, a clinical trial was designed to investigate the effects of a dietary intervention on blood vessel properties in people with peripheral arterial disease. Participants in the Canola-PAD Study consumed 25 g/day of canola oil or a Western diet oil mixture as part of their usual diet for 8 weeks. Although the intervention altered phospholipid fatty acids, vascular function, the lipid profile and inflammatory markers stayed relatively stable. Overall, this research demonstrates that dieta

Pea protein hydrolysate (PPH) has antihypertensive effects and prostanoids have been implicated in renal diseases. To investigate the role of PPH and prostanoids on renal and cardiovascular effects in cardio-renal disease, normal and diseased Han:SPRD-cy rats were given diets containing either 0, 0.5% or 1% PPH for 8 weeks. At termination, diseased rat kidneys displayed increased renal cyst growth, fibrosis, plasma creatinine and lower monocyte chemoattractant protein-1. Diseased rats also exhibited left ventricular (LV) hypertrophy, elevated systolic and diastolic blood pressures and LV end diastolic and systolic pressures. Four of five prostanoids were elevated in diseased rat kidneys. PPH attenuated systolic blood pressure, but not other components of the cardio-renal syndrome. PPH also increased select prostanoids in normal and diseased rats. Thus, dietary PPH attenuates hypertension in the Han:SPRD-cy rat, but does not ameliorate other components of disease, possibly due to increased prostanoid effects or an insufficient treatment length.

Dietary flaxseed intake has exhibited both cardioprotective and anti-atherogenic properties. Regardless, it remains unclear whether these beneficial effects extent to the regression of atherosclerotic plaques or the resolution of cholesterol-induced vascular contractile dysfunction. In the present study, we intended to determine whether dietary flaxseed has the capacity to ameliorate vascular function abnormalities and induce atherosclerotic plaque regression. As results from previous studies using a nutritional intervention to induce atherosclerotic regression may have been confounded by premature initiation of the intervention, an appropriate feeding regimen was developed to adequately evaluate flaxseeds’ effects on atherosclerotic plaque regression. New Zealand white rabbits were utilized in two studies. To establish clear evidence of plaque growth stabilization, animals received 4 weeks of a 1% cholesterol-supplemented diet. An initial subset of animals was immediately examined. The remaining animals were fed regular rabbit chow and examined at intervals up to 28 weeks. To ascertain flaxseeds’ effects on atherosclerotic plaque regression and vascular contractile function, animals were randomly assigned to a control group fed a regular diet for 12 weeks (Group I) or an experimental group fed a 1% cholesterol-supplemented diet for 4 weeks followed by a regular diet for 8 weeks (Group II). The control and a subset of experimental animals were examined immediately afterwards. The remaining experimental animals were given an additional 8 or 14 weeks of either a regular diet (Group III and V, respectively) or a 10% flaxseed-supplemented diet (Group IV and VI, respectively) and were examined afterwards. Cholesterol feeding followed by 8 weeks of withdrawal from cholesterol not only resulted in the development and stabilization of atherosclerotic plaques but also impaired the maximum contraction caused by norepinephrine and the relaxation response to acetylcholine. An a

Dietary fat has long been implicated in the etiology of metabolic and cardiovascular disease, and both the amount of fat and the fatty acid composition of the diet play a role in disease progression. Although national health organizations have set guidelines for the recommended intake of dietary fats, questions remain regarding the optimal dietary lipid profile for maintaining health and improving disease conditions. Whether certain types of fatty acids from plant-based oils can improve metabolic and vascular disease has been studied and debated, but not fully determined. In this study, we investigated the role of dietary fatty acids from plant-based oils, and examined their effects on metabolic and vascular disease parameters. Obese fa/fa Zucker rats were fed a diet containing flaxseed oil, which resulted in smaller adipocytes and decreased adipose tissue T-cell infiltration. Obese-prone Sprague Dawley rats were fed high-fat diets with different proportions of mono- and polyunsaturated fats. Changes were observed in adipose tissue levels of fatty acid synthase, adiponectin and fatty acid receptors GPR41 and GPR43, but other metabolic and inflammatory mediators in adipose tissue and serum remained stable. A systematic review and meta-analysis on the impact of n3 fatty acids on major cardiovascular endpoints showed that little evidence exists to support their role in peripheral arterial disease. Then again, very few studies on this topic have been conducted. To address this research gap, a clinical trial was designed to investigate the effects of a dietary intervention on blood vessel properties in people with peripheral arterial disease. Participants in the Canola-PAD Study consumed 25 g/day of canola oil or a Western diet oil mixture as part of their usual diet for 8 weeks. Although the intervention altered phospholipid fatty acids, vascular function, the lipid profile and inflammatory markers stayed relatively stable. Overall, this research demonstrates that dieta

Dietary flaxseed intake has exhibited both cardioprotective and anti-atherogenic properties. Regardless, it remains unclear whether these beneficial effects extent to the regression of atherosclerotic plaques or the resolution of cholesterol-induced vascular contractile dysfunction. In the present study, we intended to determine whether dietary flaxseed has the capacity to ameliorate vascular function abnormalities and induce atherosclerotic plaque regression. As results from previous studies using a nutritional intervention to induce atherosclerotic regression may have been confounded by premature initiation of the intervention, an appropriate feeding regimen was developed to adequately evaluate flaxseeds’ effects on atherosclerotic plaque regression. New Zealand white rabbits were utilized in two studies. To establish clear evidence of plaque growth stabilization, animals received 4 weeks of a 1% cholesterol-supplemented diet. An initial subset of animals was immediately examined. The remaining animals were fed regular rabbit chow and examined at intervals up to 28 weeks. To ascertain flaxseeds’ effects on atherosclerotic plaque regression and vascular contractile function, animals were randomly assigned to a control group fed a regular diet for 12 weeks (Group I) or an experimental group fed a 1% cholesterol-supplemented diet for 4 weeks followed by a regular diet for 8 weeks (Group II). The control and a subset of experimental animals were examined immediately afterwards. The remaining experimental animals were given an additional 8 or 14 weeks of either a regular diet (Group III and V, respectively) or a 10% flaxseed-supplemented diet (Group IV and VI, respectively) and were examined afterwards. Cholesterol feeding followed by 8 weeks of withdrawal from cholesterol not only resulted in the development and stabilization of atherosclerotic plaques but also impaired the maximum contraction caused by norepinephrine and the relaxation response to acetylcholine. An a

Global obesity is linked to chronic diseases including hypercholesterolemia, a cardiovascular disease risk factor, thus weight reduction in obesity is a key priority for combatting obesity. The cholesterol transporters ABCG5, ABCG8 and NPC1L1 mediate cholesterol trafficking across the intestinal wall, thus are important in regulating cholesterol metabolism and circulating levels. The objective of this study was to examine if single nucleotide polymorphisms (SNP) of cholesterol transporters ABCG5, ABCG8 and NPC1L1 are associated with changes in cholesterol synthesis and absorption and lipid parameters (LP) subsequent to weight loss (WtL) in overweight individuals. Eighty-nine individuals from two WtL trials (Trial A (n = 54) and Trial B (n = 35)) completed a 20-wk WtL period. After 10% WtL, lipid parameters excluding LDL-C were improved in Trial A, while all lipid parameters were ameliorated after 12% of WtL when Trial A and B were combined. Post-WtL, cholesterol synthesis (CS) was reduced; however, cholesterol absorption was not changed in either Trial A or the combined trials. Polymorphisms in ABCG8 V632A were associated with changes in TC and TG levels after WtL in both trial A and the combined data. SNPs in ABCG5 Q604E, ABCG8 T400K, were associated with changes in CS because of WtL in Trial A; however, the association is no longer seen in combined analysis. In conclusion, cardio-protective changes in LP due to weight loss were mediated by reductions in CS. Additionally, polymorphisms in ABCG8 were associated with amelioration in LP after WtL. Thus, the benefits in CVD risk subsequent to weight loss vary across individuals due to genetic factors associated with cholesterol trafficking.

Dietary flaxseed has cardioprotective effects that may be achieved through its rich content of the omega-3 fatty acid, alpha linolenic acid (ALA). We investigated the effects of dietary flaxseed both with and without an atherogenic cholesterol-enriched diet to determine the effects of dietary flaxseed on the expression of the adipose cytokines leptin and adiponectin. Rabbits were fed one of four diets: a regular (RG) diet, or a regular diet with added 0.5% cholesterol (CH), or 10% ground flaxseed (FX), or both (CF) for 8 weeks. Levels of leptin and adiponectin expression were assessed by RT-PCR in visceral adipose tissue. Consumption of flaxseed significantly increased plasma and adipose levels of ALA. Leptin, but not adiponectin, mRNA expression was lower in CH animals and was elevated in CF animals. Changes in leptin expression were strongly and positively correlated with adipose ALA levels and inversely correlated with levels of en face atherosclerosis. Our data demonstrate that the type of fat in the diet as well as its caloric content can specifically influence leptin expression. The findings support the hypothesis that the beneficial cardiovascular effects associated with flaxseed consumption may be related to a change in leptin expression.

Reducing consumption of fat is recommended for obese individuals; however, altering dietary fat, without reducing total fat, may modify obesity-associated consequences. The effects of dietary fat composition on obesity and insulin resistance in diet-induced obese rats were investigated. Rats were fed a high-fat lard-based diet for 12 weeks and then were randomized into one of six high-fat treatment groups (oils used: high-oleic canola, conventional canola, high-oleic/conventional canola mix, conventional canola/flax mix, safflower, or soybean) or kept on the lard diet for 8 weeks. Diets had varying effects on lipidemia and glycemia; however, insulin tolerance tests, oral glucose tolerance tests, and the skeletal muscle response to insulin were not different among groups. Muscle phospholipids showed expected differences in fatty acid (FA) composition, but polyunsaturated/saturated FA ratios were not different among groups. Overall, a consistent response to high-fat diets was observed which may be attributed to the robustness of polyunsaturated/saturated FA ratios of muscle phospholipids.

Dietary flaxseed has cardioprotective effects that may be achieved through its rich content of the omega-3 fatty acid, alpha linolenic acid (ALA). We investigated the effects of dietary flaxseed both with and without an atherogenic cholesterol-enriched diet to determine the effects of dietary flaxseed on the expression of the adipose cytokines leptin and adiponectin. Rabbits were fed one of four diets: a regular (RG) diet, or a regular diet with added 0.5% cholesterol (CH), or 10% ground flaxseed (FX), or both (CF) for 8 weeks. Levels of leptin and adiponectin expression were assessed by RT-PCR in visceral adipose tissue. Consumption of flaxseed significantly increased plasma and adipose levels of ALA. Leptin, but not adiponectin, mRNA expression was lower in CH animals and was elevated in CF animals. Changes in leptin expression were strongly and positively correlated with adipose ALA levels and inversely correlated with levels of en face atherosclerosis. Our data demonstrate that the type of fat in the diet as well as its caloric content can specifically influence leptin expression. The findings support the hypothesis that the beneficial cardiovascular effects associated with flaxseed consumption may be related to a change in leptin expression.

Reducing consumption of fat is recommended for obese individuals; however, altering dietary fat, without reducing total fat, may modify obesity-associated consequences. The effects of dietary fat composition on obesity and insulin resistance in diet-induced obese rats were investigated. Rats were fed a high-fat lard-based diet for 12 weeks and then were randomized into one of six high-fat treatment groups (oils used: high-oleic canola, conventional canola, high-oleic/conventional canola mix, conventional canola/flax mix, safflower, or soybean) or kept on the lard diet for 8 weeks. Diets had varying effects on lipidemia and glycemia; however, insulin tolerance tests, oral glucose tolerance tests, and the skeletal muscle response to insulin were not different among groups. Muscle phospholipids showed expected differences in fatty acid (FA) composition, but polyunsaturated/saturated FA ratios were not different among groups. Overall, a consistent response to high-fat diets was observed which may be attributed to the robustness of polyunsaturated/saturated FA ratios of muscle phospholipids.

Global obesity is linked to chronic diseases including hypercholesterolemia, a cardiovascular disease risk factor, thus weight reduction in obesity is a key priority for combatting obesity. The cholesterol transporters ABCG5, ABCG8 and NPC1L1 mediate cholesterol trafficking across the intestinal wall, thus are important in regulating cholesterol metabolism and circulating levels. The objective of this study was to examine if single nucleotide polymorphisms (SNP) of cholesterol transporters ABCG5, ABCG8 and NPC1L1 are associated with changes in cholesterol synthesis and absorption and lipid parameters (LP) subsequent to weight loss (WtL) in overweight individuals. Eighty-nine individuals from two WtL trials (Trial A (n = 54) and Trial B (n = 35)) completed a 20-wk WtL period. After 10% WtL, lipid parameters excluding LDL-C were improved in Trial A, while all lipid parameters were ameliorated after 12% of WtL when Trial A and B were combined. Post-WtL, cholesterol synthesis (CS) was reduced; however, cholesterol absorption was not changed in either Trial A or the combined trials. Polymorphisms in ABCG8 V632A were associated with changes in TC and TG levels after WtL in both trial A and the combined data. SNPs in ABCG5 Q604E, ABCG8 T400K, were associated with changes in CS because of WtL in Trial A; however, the association is no longer seen in combined analysis. In conclusion, cardio-protective changes in LP due to weight loss were mediated by reductions in CS. Additionally, polymorphisms in ABCG8 were associated with amelioration in LP after WtL. Thus, the benefits in CVD risk subsequent to weight loss vary across individuals due to genetic factors associated with cholesterol trafficking.

Background: Cardiac hypertrophy is a compensatory enlargement of the heart in response to stress such as hypertension. It is beneficial in reducing stress placed on the heart. However, when the stress is of a chronic nature, it becomes pathological and leads to cardiac dysfunction and heart failure. Current treatments for hypertension and heart failure have proven beneficial but are not highly specific and associated with side effects. Accordingly, there is an important need for alternative strategies to provide safe and effective treatment. Methods: Ten-week-old male spontaneously hypertensive rats (SHRs) and Wistar–Kyoto (WKY) rats were treated with resveratrol (2.5mg/kg/day) for a period of 10 weeks. Systolic blood pressure, and cardiac structure and function were measured in all groups at different time points of resveratrol treatment. Oxidative stress was also determined in all groups after 10 weeks of resveratrol treatment. Results: SHRs were characterized with high blood pressure and concentric hypertrophy from 15 weeks of age. Cardiac functional abnormalities were also evident in SHR from 15 weeks onwards. Resveratrol treatment significantly prevented the development of concentric hypertrophy, and systolic and diastolic dysfunction in SHR without lowering blood pressure. Resveratrol also significantly reduced the oxidative stress levels of cardiac tissue in SHR. Conclusions: Resveratrol treatment was beneficial in preventing the development of concentric hypertrophy and cardiac dysfunction in SHR. The cardioprotective effect of resveratrol in SHR may be partially mediated by a reduction in oxidative stress. Thus, resveratrol may have potential in preventing cardiac impairment in patients with essential hypertension.

Enlargement of adipocytes in obesity leads to alteration in adipokine production and these changes are linked to the development of obesity-related cardiovascular diseases. Adipokines specifically associated with obesity-related hypertension include angiotensinogen and adiponectin. Conjugated linoleic acid (CLA) has been reported to reduce blood pressure in obese insulin-resistant rats, but its mechanism of action has not been identified. The objective of this study was to determine whether CLA’s ability to improve obesity-related hypertension involves reducing adipocyte size and altering adipokine production. Fa/fa Zucker rats (6 or 16 week old) were fed diets containing CLA isomers for 8 weeks. The trans(t)10,cis(c)12-CLA isomer reduced adipocyte size in both younger and older rats. Despite beneficial changes in cell size of rats fed the t10,c12-CLA isomer, there were no changes in the renin-angiotensin system or pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 or the anti-inflammatory cytokine IL-10. In contrast, the t10,c12-CLA isomer increased adiponectin levels both in the circulation and in adipose tissue. This was associated with increased phosphorylation of endothelial nitric oxide synthase (eNOS) in adipose tissue and aorta. Direct treatment of CLA isomers in cultured endothelial cells did not increase eNOS phosphorylation but increases were observed with adiponectin treatment. In vivo, infusion with adiponectin increased eNOS phosphorylation in adipose of fa/fa Zucker rats in parallel with improvements in blood pressure. Similarly, when circulating levels of adiponectin increased in rats fed the t10,c12-CLA isomer diet, blood pressure was also attenuated. In younger rats, both the t10-c12 and c9,t11-CLA isomers were significantly different from the control group at week 8, however, only the t10,c12-CLA isomer was comparable to the commonly used anti-hypertensive medication captopril. In conclusion, the beneficial

Enlargement of adipocytes in obesity leads to alteration in adipokine production and these changes are linked to the development of obesity-related cardiovascular diseases. Adipokines specifically associated with obesity-related hypertension include angiotensinogen and adiponectin. Conjugated linoleic acid (CLA) has been reported to reduce blood pressure in obese insulin-resistant rats, but its mechanism of action has not been identified. The objective of this study was to determine whether CLA’s ability to improve obesity-related hypertension involves reducing adipocyte size and altering adipokine production. Fa/fa Zucker rats (6 or 16 week old) were fed diets containing CLA isomers for 8 weeks. The trans(t)10,cis(c)12-CLA isomer reduced adipocyte size in both younger and older rats. Despite beneficial changes in cell size of rats fed the t10,c12-CLA isomer, there were no changes in the renin-angiotensin system or pro-inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 or the anti-inflammatory cytokine IL-10. In contrast, the t10,c12-CLA isomer increased adiponectin levels both in the circulation and in adipose tissue. This was associated with increased phosphorylation of endothelial nitric oxide synthase (eNOS) in adipose tissue and aorta. Direct treatment of CLA isomers in cultured endothelial cells did not increase eNOS phosphorylation but increases were observed with adiponectin treatment. In vivo, infusion with adiponectin increased eNOS phosphorylation in adipose of fa/fa Zucker rats in parallel with improvements in blood pressure. Similarly, when circulating levels of adiponectin increased in rats fed the t10,c12-CLA isomer diet, blood pressure was also attenuated. In younger rats, both the t10-c12 and c9,t11-CLA isomers were significantly different from the control group at week 8, however, only the t10,c12-CLA isomer was comparable to the commonly used anti-hypertensive medication captopril. In conclusion, the beneficial

Background: Cardiac hypertrophy is a compensatory enlargement of the heart in response to stress such as hypertension. It is beneficial in reducing stress placed on the heart. However, when the stress is of a chronic nature, it becomes pathological and leads to cardiac dysfunction and heart failure. Current treatments for hypertension and heart failure have proven beneficial but are not highly specific and associated with side effects. Accordingly, there is an important need for alternative strategies to provide safe and effective treatment. Methods: Ten-week-old male spontaneously hypertensive rats (SHRs) and Wistar–Kyoto (WKY) rats were treated with resveratrol (2.5mg/kg/day) for a period of 10 weeks. Systolic blood pressure, and cardiac structure and function were measured in all groups at different time points of resveratrol treatment. Oxidative stress was also determined in all groups after 10 weeks of resveratrol treatment. Results: SHRs were characterized with high blood pressure and concentric hypertrophy from 15 weeks of age. Cardiac functional abnormalities were also evident in SHR from 15 weeks onwards. Resveratrol treatment significantly prevented the development of concentric hypertrophy, and systolic and diastolic dysfunction in SHR without lowering blood pressure. Resveratrol also significantly reduced the oxidative stress levels of cardiac tissue in SHR. Conclusions: Resveratrol treatment was beneficial in preventing the development of concentric hypertrophy and cardiac dysfunction in SHR. The cardioprotective effect of resveratrol in SHR may be partially mediated by a reduction in oxidative stress. Thus, resveratrol may have potential in preventing cardiac impairment in patients with essential hypertension.