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BACKGROUND. Activation of the NLRP3 inflammasome is associated with metabolic dysfunction, and intermittent fasting has been shown to improve clinical presentation of NLRP3 inflammasome–linked diseases. As mitochondrial perturbations, which function as a damage-associated molecular pattern, exacerbate NLRP3 inflammasome activation, we investigated whether fasting blunts inflammasome activation via sirtuin-mediated augmentation of mitochondrial integrity.METHODS. We performed a clinical study of 19 healthy volunteers. Each subject underwent a 24-hour fast and then was fed a fixed-calorie meal. Blood was drawn during the fasted and fed states and analyzed for NRLP3 inflammasome activation. We enrolled an additional group of 8 healthy volunteers to assess the effects of the sirtuin activator, nicotinamide riboside, on NLRP3 inflammasome activation.RESULTS. In the fasting/refeeding study, individuals showed less NLRP3 inflammasome activation in the fasted state compared with that in refed conditions. In a human macrophage line, depletion of the mitochondrial-enriched sirtuin deacetylase SIRT3 increased NLRP3 inflammasome activation in association with excessive mitochondrial ROS production. Furthermore, genetic and pharmacologic SIRT3 activation blunted NLRP3 activity in parallel with enhanced mitochondrial function in cultured cells and in leukocytes extracted from healthy volunteers and from refed individuals but not in those collected during fasting.CONCLUSIONS. Together, our data indicate that nutrient levels regulate the NLRP3 inflammasome, in part through SIRT3-mediated mitochondrial homeostatic control. Moreover, these results suggest that deacetylase-dependent inflammasome attenuation may be amenable to targeting in human disease.TRIAL REGISTRATION. ClinicalTrials.gov NCT02122575 and NCT00442195.FUNDING. Division of Intramural Research, NHLBI of the NIH.

Background: This study aims to examine the effects of green tea extract (GTE) supplement on overweight and obese women with high levels of low density lipoprotein-cholesterol (LDL-C).Methods: The randomized, double-blind, crossover and placebo-controlled clinical trial was conducted from August 2012 to December 2013. Seventy-three out of 90 subjects aged between 18 and 65 years, with body mass index (BMI) ≥ 27 kg/m2 and LDL-C ≥ 130 mg/dl were included in the analysis. The subjects were randomly divided into Groups A and B. Group A received GTE supplement treatment for the first 6 weeks, while Group B received placebo daily. After 6 weeks of treatment and 14 days of washout period, Group A switched to placebo and Group B switched to GTE treatment for 6 weeks. The reduction of LDL-C level between treatments was assessed as the outcome. Additionally, anthropometric measurements, plasma lipoproteins and hormone peptides of both groups were measure at the beginning of weeks 6, 8, and 14 after treatment.Results: Subjects treated with GTE (n = 73) for 6 weeks showed significant differences, with 4.8% (p = 0.048) reduction in LDL-C and 25.7% (p = 0.046) increase in leptin. However, there was no statistical difference in the levels of total cholesterol, triglyceride and high density lipoprotein between the GTE and placebo groups after treatments.Conclusions: This study shows that green tea extract effectively increases leptin and reduces LDL in overweight and obese women after 6 weeks of treatment even though there were no significant changes in other biochemical markers related to overweight.