Progress 02/01/15 to 01/31/18
Outputs
Target Audience:Individuals who are interested in nutrition and health as it relates to HDL metabolism, obesity, diabetes, and cardiovascular disease. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Graduate students were involved and trained in conducting experiments and in the writing and submission of a journal article and research conference abstract. How have the results been disseminated to communities of interest?Findings have been submitted for presentation at the American Society for Nutrition meeting in June 2018, as well as at the USDA Project Directors Meeting which also takes place in June 2018. Furthermore, a manuscript of the research findings was submitted and is currently under review in a peer-reviewed journal. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Low levels of high-density lipoprotein cholesterol (HDL-C) have been correlated with increased risk for heart disease in epidemiological studies. However, drug therapies targeting an increase in HDL-C concentrations have failed to demonstrate a reduced risk. More recently, HDL particle functionality rather than HDL-C concentration, has been suggested to be a better predictor of heart disease risk. In certain chronic inflammatory diseases like atherosclerosis, normally protective HDL particles become dysfunctional and may actually worsen disease outcomes. In light of increasing heart disease incidence in the U.S., there is a need to identify novel dietary approaches aimed at preventing HDL dysfunction and inflammation associated with these chronic diseases. Ingestion of bioactive dietary components, such as polyphenols, may increase both HDL-C concentration and HDL functionality. Dietary anthocyanins have been shown to reduce inflammation in animal models and may ameliorate inflammation-related complications, such as atheroclerosis. Anthocyanins are rarely consumed in isolation, so it is important to examine their effects in combination with other potential bioactives in foods, as there may be other factors that influence their overall impact on atherosclerosis. Black elderberry (Sambucus nigra) contains high amounts of anthocyanins (~1300 mg/100 g), a subclass of polyphenols, relative to other edible berries. We investigated whether the consumption of a black elderberry extract (BEE) influenced lipid metabolism, HDL functionality, and atherosclerosis in a mouse model of hypercholesterolemia (apoE-/- mice). We fed male apoE-/- (n = 12/group) ad libitum a low-fat AIN-93M diet supplemented with 0, 0.25% or 1% (by weight of diet; 0, ~40, and ~150 mg anthocyanins/kg body weight, respectively) black elderberry extract (BEE) for 24 weeks. Feeding 1% BEE increased total serum cholesterol (+31%) and non-HDL cholesterol (+32%) compared to control diet. PON1 arylesterase (+32%) and lactonase (+45%) activities also increased with the 1% BEE diet. Both 0.25% BEE and 1% BEE diets strongly increased HDL cholesterol efflux capacity (CEC) by 64% and 85%, respectively. Further, BEE dose-dependently lowered serum liver enzymes and hepatic inflammatory gene expression. However, there were no differences between groups in atherosclerosis development assessed by aortic root and en face aortic lesion areas. The current data suggest that chronic BEE supplementation in apoE-/- mice dose-dependently improved HDL function (PON1 activity and HDL CEC). However, BEE also promoted hyperlipidemia, which likely offset HDL effects, resulting in no differences in atherosclerosis development compared to control.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Millar C, Duclos Q, Blesso CN. Effects of dietary flavonoids on reverse cholesterol transport, HDL metabolism, and HDL function. Adv Nutr. 2017 Mar 15;8(2):226-239. doi: 10.3945/an.116.014050.
- Type:
Journal Articles
Status:
Under Review
Year Published:
2018
Citation:
Millar CL, Norris GH, Jiang C, Kry J, Vitols A, Garcia C, Park YK, Lee JY, Blesso CN. Long-term supplementation of black elderberry extract improves HDL function, but promotes hyperlipidemia with no effect on atherosclerosis development in apolipoprotein E-knockout mice. 2018.
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2018
Citation:
Millar CM, Norris GH, Jiang C, Garcia C, Blesso CN. Black elderberry extract improves HDL function in atherosclerosis-prone mice. Accepted to Nutrition 2018 conference. Boston, MA.
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Progress 02/01/16 to 01/31/17
Outputs
Target Audience:Individuals who are interested in nutrition and health as it relates to HDL metabolism, obesity, diabetes, and cardiovascular disease. Changes/Problems:We have extended the award so that the new project end date is 01/31/2018 (no-cost extension). This will allow us to finish the rest of the project objectives related to the atherosclerosis outcomes. What opportunities for training and professional development has the project provided?Graduate students were involved and trained in conducting experiments and in the writing and submission of a journal article and research conference abstract. How have the results been disseminated to communities of interest?Findings have been submitted for presentation at the Experimental Biology meeting in April, 2017 and a manuscript was submitted and is currently under review. What do you plan to do during the next reporting period to accomplish the goals?Results of the project will be presented at the Experimental Biology meeting and other scientific meetings. Manuscripts will be published in peer-reviewed scientific journals to disseminate our findings to the scientific community.
Impacts
What was accomplished under these goals?
Low levels of high-density lipoprotein cholesterol (HDL-C) have been correlated with increased risk for heart disease in epidemiological studies. However, drug therapies targeting an increase in HDL-C concentrations have failed to demonstrate a reduced risk. More recently, HDL particle functionality rather than HDL-C concentration, has been suggested to be a better predictor of heart disease risk. In certain chronic inflammatory diseases like atherosclerosis, normally protective HDL particles become dysfunctional and may actually worsen disease outcomes. In light of increasing heart disease incidence in the U.S., there is a need to identify novel dietary approaches aimed at preventing HDL dysfunction and inflammation associated with these chronic diseases. Ingestion of bioactive dietary components, such as polyphenols, may increase both HDL-C concentration and HDL functionality. Dietary anthocyanins have been shown to reduce inflammation in animal models and may ameliorate inflammation-related complications, such as atheroclerosis. Black elderberry (Sambucus nigra) contains high amounts of anthocyanins (~1300 mg/100 g), a subclass of polyphenols, relative to other edible berries. We investigated whether the consumption of a black elderberry extract (BEE) influenced lipid metabolism, HDL functionality, and atherosclerosis in a mouse model of hypercholesterolemia (apoE-/- mice). We fed male apoE-/- (n = 12/group) ad libitum a low-fat AIN-93M diet supplemented with 0, 0.25% or 1% (by weight of diet; 0, ~40, and ~150 mg anthocyanins/kg body weight, respectively) black elderberry extract (BEE) for 24 weeks. Supplementation with 1% BEE significantly increased total cholesterol (+31.5%) and HDL-C (+26%), while triglycerides were not significantly changed. Paraoxonase-1 (PON1), a lipolactonase enzyme carried by HDL which prevents lipoprotein oxidation, was increased by 32% in the 1% BEE group when compared to controls (p < 0.05). Analysis of hepatic gene expression revealed that BEE significantly increased expression of Nrf2 and GClc (p < 0.05), both of which are important for endogenous antioxidant defense and may be related to the significant reductions in serum alanine transaminase and aspartate transaminase levels in the BEE treatment group (p < 0.05). Despite improved markers of HDL-C and HDL function, en face analysis of aortas showed no difference in severity of atherosclerosis between groups. The current data suggests that BEE supplementation improves HDL-C and HDL function, while also upregulating genes involved in the endogenous antioxidant defense.
Publications
- Type:
Journal Articles
Status:
Under Review
Year Published:
2016
Citation:
Millar C, Duclos Q, Blesso CN. Effects of dietary flavonoids on reverse cholesterol transport, HDL metabolism, and HDL function. Adv Nutr. In revision.
- Type:
Conference Papers and Presentations
Status:
Submitted
Year Published:
2017
Citation:
Millar CL, Winter H, Georgelos J, Norris GH, Park YK, Blesso CN. Black Elderberry Extract Improves Serum HDL-C and Paraoxonase-1 Activity in Atherosclerosis-Prone Mice. Submitted to Experimental Biology 2017 conference. Chicago, IL.
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Progress 02/01/15 to 01/31/16
Outputs
Target Audience:Individuals who are interested in nutrition and health as it relates to HDL metabolism, obesity, diabetes, and cardiovascular disease. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Graduate students were involved and trained in conducting experiments and in presenting data. How have the results been disseminated to communities of interest?Findings were published in a peer-reviewed scientific journal. What do you plan to do during the next reporting period to accomplish the goals?Results of the project will be presented at Experimental Biology conference and other scientific meetings. Manuscripts will be published in peer-reviewed scientific journals to disseminate our findings to the scientific community.
Impacts
What was accomplished under these goals?
In certain chronic inflammatory diseases like obesity and atherosclerosis, normally protective HDL particles become dysfunctional and may actually worsen disease outcomes. In light of increasing obesity and heart disease incidence in the U.S., there is a need to identify novel dietary approaches aimed at preventing HDL dysfunction and inflammation associated with these chronic diseases. Dietary anthocyanins have been shown to reduce inflammation in animal models and may ameliorate obesity-related complications. We investigated the metabolic effects of anthocyanin-rich black elderberry extract (BEE) in a diet-induced obese C57BL/6J mouse model. Mice were fed either a low-fat diet (n = 8), high-fat lard-based diet (HFD; n = 16), HFD+0.25 % (w/w) BEE (0.25 %-BEE; n = 16) or HFD+1.25 % BEE (1.25 %-BEE; n = 16) for 16 weeks. After 16 weeks, both BEE groups had significantly lower liver weights, serum triglycerides, homoeostasis model assessment and serum monocyte chemoattractant protein-1 compared with HFD. The 0.25 %-BEE also had lower serum insulin and TNFα compared with HFD. Hepatic fatty acid synthase mRNA was lower in both BEE groups, whereas PPARγ2 mRNA and liver cholesterol were lower in 1.25 %-BEE, suggesting decreased hepatic lipid synthesis. Higher adipose PPARγ mRNA, transforming growth factor β mRNA and adipose tissue histology suggested a pro-fibrogenic phenotype that was less inflammatory in 1.25 %-BEE. Skeletal muscle mRNA expression of the myokine IL-6 was higher in 0.25 %-BEE relative to HFD. These results suggest that BEE may have improved some metabolic disturbances present in this mouse model of obesity by lowering serum triglycerides, inflammatory markers and insulin resistance.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
Farrell N, Norris G, Ryan J, Porter CM, Jiang C, Blesso CN. Black elderberry extract attenuates inflammation and metabolic dysfunction in diet-Induced obese mice. Br J Nutr. 2015 Aug 28:1-9.
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