Proteome from patients with metabolic syndrome is regulated by quantity and quality of dietary lipids.

BACKGROUND: Metabolic syndrome is a multi-component disorder associated to a high risk of cardiovascular disease. Its etiology is the result of a complex interaction between genetic and environmental factors, including dietary habits. We aimed to identify the target proteins modulated by the long-term consumption of four diets differing in the quality and quantity of lipids in the whole proteome of peripheral blood mononuclear cells (PBMC). RESULTS: A randomized, controlled trial conducted within the LIPGENE study assigned 24 MetS patients for 12 weeks each to 1 of 4 diets: a) high-saturated fatty acid (HSFA), b) high-monounsaturated fatty acid (HMUFA), c) low-fat, high-complex carbohydrate diets supplemented with placebo (LFHCC) and d) low-fat, high-complex carbohydrate diets supplemented with long chain (LC) n-3 polyunsaturated fatty acids (PUFA) (LFHCC n-3). We analyzed the changes induced in the proteome of both nuclear and cytoplasmic fractions of PBMC using 2-D proteomic analysis. Sixty-seven proteins were differentially expressed after the long-term consumption of the four diets. The HSFA diet induced the expression of proteins responding to oxidative stress, degradation of ubiquitinated proteins and DNA repair. However, HMUFA, LFHCC and LFHCC n-3 diets down-regulated pro-inflammatory and oxidative stress-related proteins and DNA repairing proteins. CONCLUSION: The long-term consumption of HSFA, compared to HMUFA, LFHCC and LFHCC n-3, seems to increase the cardiovascular disease (CVD) risk factors associated with metabolic syndrome, such as inflammation and oxidative stress, and seem lead to DNA damage as a consequence of high oxidative stress.

Effects of the Mediterranean diet supplemented with coenzyme q10 on metabolomic profiles in elderly men and women.

BACKGROUND: Characterization of the variations in the metabolomic profiles of elderly people is a necessary step to understand changes associated with aging. This study assessed whether diets with different fat quality and supplementation with coenzyme Q10 (CoQ) affect the metabolomic profile in urine analyzed by proton nuclear magnetic resonance spectroscopy from elderly people. METHODS: Ten participants received, in a cross-over design, four isocaloric diets for 4-week periods each: Mediterranean diet supplemented with CoQ (Med + CoQ diet); Mediterranean diet; Western diet rich in saturated fat diet; low-fat, high-carbohydrate diet enriched in n-3 polyunsaturated fat. RESULTS: Multivariate analysis showed differences between diets when comparing Med + CoQ diet and saturated fat diet, with greater hippurate urine levels after Med + CoQ diet and higher phenylacetylglycine levels after saturated fat diet in women. Following consumption of Med + CoQ, hippurate excretion was positively correlated with CoQ and ß-carotene plasma levels and inversely related to Nrf2, thioredoxin, superoxide dismutase 1, and gp91(phox) subunit of NADPH oxidase gene expression. After saturated fat diet consumption, phenylacetylglycine excretion was inversely related to CoQ plasma level and positively correlated with isoprostanes urinary level. CONCLUSIONS: The association between hippurate excretion and antioxidant biomarkers along with the relationship between phenylacetylglycine excretion and oxidant biomarkers suggests that the long-term consumption of a Med + CoQ diet could be beneficial for healthy aging and a promising challenge in the prevention of processes related to chronic oxidative stress, such as cardiovascular and neurodegenerative disease.

Influence of endothelial dysfunction on telomere length in subjects with metabolic syndrome: LIPGENE study.

Previous evidences support that increased oxidative stress (OxS) may play an important role in metabolic syndrome (MetS) and both are closely linked to vascular dysfunction. This study determined whether there is a relationship between endothelial function and relative telomere length (RTL) in MetS subjects. In this cross-sectional study from the LIPGENE cohort, a total of 88 subjects (36 men and 52 women) were divided into four groups by quartiles of telomere length. We measured ischemic reactive hyperemia (IRH), total nitrite (NO) and protein carbonyl (PC) plasma levels, F2-isoprostanes urinary levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) plasma activities. IRH and NO plasma levels were higher in subjects with longer RTL (quartiles 3 and 4), while PC plasma levels, F2-isoprostanes urinary levels, and GPx and SOD plasma activities were lower in quartile 4 subjects (longest RTL). Additionally, MetS subjects with longer RTL had greater homeostatic model assessment-ß level and lower triglycerides plasma levels. Our results suggest that endothelial dysfunction, associated with high levels of OxS, could be entailed in an increment of telomere attrition. Thus, further support of the molecular and cellular mechanisms involved in vascular dysfunction may contribute to the development of strategies to decelerate vascular aging or prevent cardiovascular disease.

Dietary fat modifies lipid metabolism in the adipose tissue of metabolic syndrome patients.

Adipose tissue (AT) is a key organ in the regulation of total body lipid homeostasis, which is responsible for the storage and release of fatty acids according to metabolic needs. We aimed to investigate the effect of the quantity and quality of dietary fat on the lipogenesis and lipolysis processes in the AT of metabolic syndrome (MetS) patients. A randomized, controlled trial conducted within the LIPGENE study assigned MetS patients to one of four diets: (a) high-saturated fatty acid (HSFA) (b) high-monounsaturated fatty acid, and (c, d) two low-fat, high-complex carbohydrate diets supplemented with long chain (LC) n-3 (LFHCC n-3) polyunsaturated fatty acids (PUFA) or placebo (LFHCC), for 12 weeks each. A fat challenge reflecting the same fatty acid composition as the original diets was conducted post-intervention. Long-term consumption of the LFHCC diet induced an increase in the fasting expression levels of the sterol regulatory element binding protein-1 and stearoyl-CoA desaturase D9-desaturase genes, whereas the supplementation of this diet with n-3 PUFA reversed this effect (p = 0.007). In contrast, long-term consumption of the HSFA diet increased the expression of the adipose triglyceride lipase (ATGL) gene, at both fasting and postprandial states (both, p < 0.001). Our results showed the anti-lipogenic effect exerted by LC n-3 PUFA when administered together with a LFHCC diet. Conversely, a diet high in saturated fat increased the expression of the lipolytic gene ATGL relative to the other diets.

Polymorphism at the TNF-alpha gene interacts with Mediterranean diet to influence triglyceride metabolism and inflammation status in metabolic syndrome patients: From the CORDIOPREV clinical trial.

SCOPE: To examine whether the consumption of a Mediterranean diet (MedDiet), compared with a low-fat diet, interacts with two single nucleotide polymorphisms at the tumor necrosis factor alpha gene (rs1800629, rs1799964) in order to improve triglycerides (TG), glycemic control, and inflammation markers. METHODS AND RESULTS: Genotyping, biochemical measurements, dietary intervention, and oral fat load test meal were determined in 507 metabolic syndrome (MetS) patients selected from all the subjects included in CORDIOPREV clinical trial (n = 1002). At baseline, G/G subjects (n = 408) at the rs1800629 polymorphism, showed higher fasting and postprandial TG (p = 0.003 and p = 0.025, respectively), and high sensitivity C-reactive protein (hsCRP) (p = 0.003) plasma concentrations than carriers of the minor A-allele (G/A + A/A) (n = 99). After 12 months of MedDiet, baseline differences between genotypes disappeared. The decrease in TG and hsCRP was statistically significant in G/G subjects (n = 203) compared with carriers of the minor A-allele (p = 0.005 and p = 0.034, respectively) (n = 48). No other gene-diet interactions were observed in either diet. CONCLUSION: These results suggest that the rs1800629 at the tumor necrosis factor alpha gene interacts with MedDiet to influence TG metabolism and inflammation status in MetS subjects. Understanding the role of gene-diet interactions may be the best strategy for personalized treatment of MetS.

Postprandial antioxidant gene expression is modified by Mediterranean diet supplemented with coenzyme Q(10) in elderly men and women.

Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. We have investigated whether the quality of dietary fat alters postprandial gene expression and protein levels involved in oxidative stress and whether the supplementation with coenzyme Q(10) (CoQ) improves this situation in an elderly population. Twenty participants were randomized to receive three isocaloric diets each for 4 weeks: Mediterranean diet supplemented with CoQ (Med + CoQ diet), Mediterranean diet (Med diet), saturated fatty acid-rich diet (SFA diet). After 12-h fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Nrf2, p22(phox) and p47(phox), superoxide dismutase 1 and 2 (SOD1 and SOD2), glutathione peroxidase 1 (GPx1), thiorredoxin reductase (TrxR) gene expression and Kelch-like ECH associating protein 1 (Keap-1) and citoplasmic and nuclear Nrf2 protein levels were determined. Med and Med + CoQ diets induced lower Nrf2, p22(phox), p47(phox), SOD1, SOD2 and TrxR gene expression and higher cytoplasmic Nrf2 and Keap-1 protein levels compared to the SFA diet. Moreover, Med + CoQ diet produced lower postprandial Nrf2 gene expression and lower nuclear Nrf2 protein levels compared to the other diets and lower GPx1 gene expression than the SFA diet. Our results support the antioxidant effect of a Med diet and that exogenous CoQ supplementation has a protective effects against free radical overgeneration through the lowering of postprandial oxidative stress modifying the postprandial antioxidant protein levels and reducing the postprandial expression of antioxidant genes in peripheral blood mononuclear cells.

Mediterranean diet supplemented with coenzyme Q10 modifies the expression of proinflammatory and endoplasmic reticulum stress-related genes in elderly men and women.

We have investigated whether the quality of dietary fat and supplementation with coenzyme Q(10) (CoQ) modifies expression of genes related with inflammatory response and endoplasmic reticulum stress in elderly persons. Twenty participants received three diets for 4 weeks each: Mediterranean diet + CoQ (Med + CoQ), Mediterranean diet (Med), and saturated fatty acid-rich diet (SFA). After 12-hour fast, volunteers consumed a breakfast with a fat composition similar to that consumed in each of the diets. Med and Med + CoQ diets produced a lower fasting calreticulin, IL-1b, and JNK-1 gene expression; a lower postprandial p65, IKK-b, MMP-9, IL-1b, JNK-1, sXBP-1, and BiP/Grp78 gene expression; and a higher postprandial IkB-a gene expression compared with the SFA diet. Med + CoQ diet produced a lower postprandial decrease p65 and IKK-b gene expression compared with the other diets. Our results support the anti-inflammatory effect of Med diet and that exogenous CoQ supplementation in synergy with a Med diet modulates the inflammatory response and endoplasmic reticulum stress.