ABSTRACT
Myricetin is a naturally occurring flavonol found in many plant based food sources. It increases the lifespan of Caenorhabditis elegans, but the molecular mechanisms are not yet fully understood. We have investigated the impact of this flavonoid on the transcription factors DAF-16 (C. elegans FoxO homologue) and SKN-1 (Nrf2 homologue), which have crucial functions in the regulation of ageing. Myricetin is rapidly assimilated by the nematode, causes a nuclear translocation of DAF-16 but not of SKN-1, and finally prolongs the mean adult lifespan of C. elegans by 32.9%. The lifespan prolongation was associated with a decrease in the accumulation of reactive oxygen species (ROS) detected by DCF. Myricetin also decreases the formation of lipofuscin, a pigment consisting of highly oxidized and cross-linked proteins that is considered as a biomarker of ageing in diverse species. The lifespan extension was completely abolished in a daf-16 loss-of-function mutant strain (CF1038). Consistently with this result, myricetin was also not able to diminish stress-induced ROS accumulation in the mutant. These results strongly indicate that the pro-longevity effect of myricetin is dependent on DAF-16 and not on direct anti-oxidative effects of the flavonoid.
Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/physiology , Flavonoids/pharmacology , Forkhead Transcription Factors/metabolism , Longevity/drug effects , Animals , Antioxidants/pharmacology , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/metabolism , Caloric Restriction , Cell-Free System , Chromans , DNA-Binding Proteins/metabolism , Flavonoids/chemistry , Flavonoids/metabolism , Free Radical Scavengers/pharmacology , Green Fluorescent Proteins/metabolism , HCT116 Cells , Hot Temperature , Humans , Lipofuscin/metabolism , Oxidation-Reduction/drug effects , Protein Transport/drug effects , Reactive Oxygen Species/metabolism , Stress, Physiological/drug effects , Transcription Factors/metabolismABSTRACT
BACKGROUND: The high prevalence of metabolic syndrome (MetS) has highlighted the need for effective dietary interventions to combat this growing problem. OBJECTIVE: To assess the impact of a Mediterranean-style low-glycemic-load diet (control arm, n = 44) or the same diet plus a medical food containing phytosterols, soy protein, and extracts from hops and acacia (intervention arm, n = 45) on cardiometabolic risk variables in women with MetS. METHODS: In this 12-week, 2-arm randomized trial, baseline, week 8 and 12, fasting blood samples were drawn to measure plasma lipids, apolipoproteins, and homocysteine. Dietary records were also collected and analyzed. RESULTS: There were decreases in fat and sugar intake (P < .001 for both) and increases in docosahexaenoic acid and eicosapentaenoic acid intake (P < .001 for both) over time, consistent with the prescribed diet. Regarding MetS variables, there were decreases in waist circumference, systolic and diastolic blood pressure, and plasma triglycerides in all subjects (P < .001 for all) with no differences between arms. Plasma low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein (apo) B, and apo B/apo A1 were reduced over time but to a greater extent in the intervention arm (P < .05 for all), indicating the medical food had a greater effect in altering lipoprotein metabolism. Further, medical food intake was associated with reduced plasma homocysteine (P < .01) compared to the control arm. CONCLUSION: A Mediterranean-style low-glycemic-load diet effectively reduces the variables of MetS. Addition of the medical food results in a less atherogenic lipoprotein profile and lower plasma homocysteine.
Subject(s)
Cholesterol, LDL/blood , Diet, Mediterranean , Hypercholesterolemia/diet therapy , Metabolic Syndrome/diet therapy , Adult , Aged , Apolipoproteins/blood , Blood Glucose/analysis , C-Reactive Protein/analysis , Docosahexaenoic Acids/therapeutic use , Eating , Eicosapentaenoic Acid/therapeutic use , Female , Glycemic Index , Homocysteine/blood , Humans , Middle Aged , Waist Circumference , Young AdultABSTRACT
The purpose of this study was to correlate biomarkers of metabolic syndrome (MetS), with markers of inflammation and macronutrient intake in 89 women (25-72 years) with MetS. We hypothesized that waist circumference (WC) would have the stronger correlations with inflammatory parameters and would correlate with carbohydrate intake. Values for WC (108.7 ± 11.1 cm) and plasma triglycerides (202.7 ± 52.1 mg/dL) were elevated, whereas plasma glucose levels varied from 66 to 179 mg/dL, with 42% of women having insulin resistance. Plasma levels of interleukin 6 (0.2-15.9 mg/L), tumor necrosis factor α (1.47-12.3 mg/L), and high-sensitivity C-reactive protein (0.06-3.08 mg/dL) varied widely, with most women being above values considered normal. Subjects had high intake of total sugar (92.3 ± 56.4 g/d), high glycemic index (59.8 ± 6.5), and glycemic load (127.2 ± 56.1), whereas dietary fiber (17.1 ± 9.1 g/d) was below recommended intake. Waist circumference was positively correlated with insulin (r = 0.275, P < .01) and with the inflammatory markers interleukin 6 (r = 0.307, P < .01) and tumor necrosis factor α (r = 0.228, P < .05) and negatively correlated with plasma adiponectin (r = -0.309, P < .0001). In addition, WC was positively correlated with total carbohydrate, added sugar, and glycemic load (P < .05) but not with fat or protein. These results are consistent with central obesity being a key marker of the inflammatory state, and they also suggest that carbohydrates, particularly those that are digested rapidly, contribute to increased risk of central obesity and development of MetS.