Nutraceutical therapies for atherosclerosis

Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries and is considered to be a major underlying cause of cardiovascular disease (CVD). Although the development of pharmacotherapies to treat CVD has contributed to a decline in cardiac mortality in the past few decades, CVD is estimated to be the cause of one-third of deaths globally. Nutraceuticals are natural nutritional compounds that are beneficial for the prevention or treatment of disease and, therefore, are a possible therapeutic avenue for the treatment of atherosclerosis. The purpose of this Review is to highlight potential nutraceuticals for use as antiatherogenic therapies with evidence from in vitro and in vivo studies. Furthermore, the current evidence from observational and randomized clinical studies into the role of nutraceuticals in preventing atherosclerosis in humans will also be discussed

Abstract 60: The ABCG5 ABCG8 Sterol Transporter Opposes Insulin Resistance and Fatty Liver Disease Independent of Phytosterol Accumulation

ABCG5 and ABCG8 form a complex (G5G8) that opposes the absorption of plant sterols, but is also expressed in liver where it promotes the excretion of cholesterol into bile. Hepatic G5G8 is transcriptionally regulated by a number of factors implicated in the development of insulin resistance and nonalcoholic fatty liver disease (NAFLD). Therefore, we hypothesized that G5G8 may influence the development of diet-induced obesity phenotypes independently of its role in opposing phytosterol absorption. G5G8 knockout (KO) mice and their wild type (WT) littermates were challenged with plant sterol free low fat (LF) or high fat (HF) diets. Weight gain and the rise in fasting glucose were accelerated in G5G8 KO mice following HF feeding. HF-fed G5G8 KO mice had increased liver weight, hepatic lipids and plasma ALT compared to WT controls. Consistent with the development of NAFLD, macrophage infiltration, the number of TUNEL positive cells and the expression of proinflammatory cytokines were also increased in G5G8 KO mice, but there was no evidence of fibrosis. Hepatic lipid accumulation was associated with increased mRNA levels for PPARγ and PPARγ target genes, but not genes involved in lipogenesis. Phosphorylation of eukaryotic translation initiation factor 2α (eiF2α) and expression activating transcription factor 4 (ATF4) and tribbles 3 (Trb3) were elevated in HF-fed G5G8 KO mice, a pathway that links the unfolded protein response (UPR) to the development if insulin resistance through inhibition of protein kinase B (Akt) phosphorylation. However, the remaining components of the UPR were unchanged. Conclusion: G5G8 plays a previously unappreciated role in the development of insulin resistance and fatty liver disease by opposing hepatic accumulation of cholesterol and phosphorylation of eiF2α. </jats:p

The pea genetic resources of the Balkans, to represent the first cultivated peas of Europe

International audienc

ABCD2 is abundant in adipose tissue and opposes the accumulation of dietary erucic acid (C22:1) in fat[S]

The ATP binding cassette transporter, ABCD2 (D2), is a peroxisomal protein whose mRNA has been detected in the adrenal, brain, liver, and fat. Although the role of this transporter in neural tissues has been studied, its function in adipose tissue remains unexplored. The level of immunoreactive D2 in epididymal fat is >50-fold of that found in brain or adrenal. D2 is highly enriched in adipocytes and is upregulated during adipogenesis but is not essential for adipocyte differentiation or lipid accumulation in day 13.5 mouse embryonic fibroblasts isolated from D2-deficient (D2−/−) mice. Although no differences were appreciated in differentiation percentage, total lipid accumulation was greater in D2−/− adipocytes compared with the wild type. These results were consistent with in vivo observations in which no significant differences in adiposity or adipocyte diameter between wild-type and D2−/− mice were observed. D2−/− adipose tissue showed an increase in the abundance of 20:1 and 22:1 fatty acids. When mice were challenged with a diet enriched in erucic acid (22:1), this lipid accumulated in the adipose tissue in a gene-dosage-dependent manner. In conclusion, D2 is a sterol regulatory element binding protein target gene that is highly abundant in fat and opposes the accumulation of dietary lipids generally absent from the triglyceride storage pool within adipose tissue