title: Green Tea Extract and Catechol-O-Methyltransferase Genotype Modify Fasting Serum Insulin and Plasma Adiponectin Concentrations in a Randomized Controlled Trial of Overweight and Obese Postmenopausal Women. Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. The plasma leptin/adiponectin ratio predicts first cardiovascular event in men: a prospective nested case-control study. Plasma adiponectin levels and risk of myocardial infarction in men. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Influence of quercetin-rich onion peel extracts on adipokine expression in the visceral adipose tissue of rats. Efficacy of an orlistat-resveratrol combination for weight loss in subjects with obesity: A randomized controlled trial. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease.
abstract: BACKGROUND Green tea consumption has been associated with favorable changes in body weight and obesity-related hormones , although it is not known whether these changes result from green tea polyphenols or caffeine . OBJECTIVE We examined the impact of decaffeinated green tea extract ( GTE ) containing 843 mg of (-)-epigallocatechin-3-gallate on anthropometric variables , obesity-associated hormones , and glucose homeostasis . METHODS The Minnesota Green Tea Trial was a 12-mo r and omized , double-blind , placebo-controlled clinical trial of 937 healthy postmenopausal women assigned to either decaffeinated GTE ( 1315 mg total catechins/d ) or a placebo  , stratified by catechol-O-methyltransferase ( COMT ) genotype . This study was conducted in a subset of 237 overweight and obese participants [ body mass index ( BMI ) ≥25 kg/m(2 ) ] . RESULTS No changes in energy intake , body weight , BMI , or waist circumference ( WC ) were observed over 12 mo in women taking GTE ( n = 117 ) or placebo ( n = 120 ) . No differences were seen in circulating leptin , ghrelin , adiponectin , or glucose concentrations at month 12 . Participants r and omly assigned to GTE with baseline insulin ≥10 μIU/mL ( n = 23 ) had a decrease in fasting serum insulin from baseline to month 12 ( -1.43 ± 0.59 μIU/mL ) , whereas those r and omly assigned to placebo with baseline insulin ≥10 μIU/mL ( n = 19 ) had an increase in insulin over 12 mo ( 0.55 ± 0.64 μIU/mL , P < 0.01 ) . Participants with the homozygous high-activity ( G/G ) form of COMT had significantly lower adiponectin ( 5.97 ± 0.50 compared with 7.58 ± 0.53 μg/mL , P = 0.03 ) and greater insulin concentrations ( 7.63 ± 0.53 compared with 6.18 ± 0.36 μIU/mL , P = 0.02 ) at month 12 compared with those with the low-activity ( A/A ) genotype , regardless of treatment group . CONCLUSIONS Decaffeinated GTE was not associated with reductions in body weight , BMI , or WC and did not alter energy intake or mean hormone concentrations in healthy postmenopausal women over 12 mo . GTE decreased fasting insulin concentrations in those with elevated baseline fasting concentrations . The high-activity form of the COMT enzyme may be associated with elevations in insulin and a reduction in adiponectin concentrations over time . This trial was registered at http://www . clinical trials.gov as NCT00917735 The polyphenol resveratrol is considered to exert many beneficial actions , such as antioxidant , anti-inflammatory , insulin-sensitizer and anticancer effects . Its benefits in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Our aims were to determine whether resveratrol supplementation at two different dosages ( 500 and 40mg/day ) for 6 months i ) reduced the concentrations of C-reactive-protein ( CRP ) and ii ) ameliorated the metabolic pattern of T2DM patients .  In the present double-blind , r and omized , placebo-controlled trial , 192 T2DM patients were r and omized to receive resveratrol 500mg/day ( Resv500arm ) , resveratrol 40mg/day ( Resv40arm ) or placebo for 6-months . At baseline and at the trial end , CRP values , anthropometric , metabolic and liver parameters were determined . No serious adverse event occurred . A dose-dependent , though not significant , CRP decrease of 5.6 % ( Resv40arm ) and 15.9 % ( Resv500arm ) was observed vs placebo . We failed to detect significant differences in weight , BMI , waist circumference , and values of arterial blood pressure , fasting glucose , glycated hemoglobin , insulin , C-peptide , free fatty acids , liver transaminases , uric acid , adiponectin , interleukin-6 , in both the Resv500 and Resv40 arms vs placebo . Total cholesterol and triglycerides slightly increased in the Resv500arm . Subgroup analyses revealed that lower diabetes duration ( in both Resv500 and Resv40arms ) , and , in the Resv500arm , younger age , aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo . The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations , nor improve the metabolic pattern of T2DM patients OBJECTIVE The plasma leptin/adiponectin ( L/A ) ratio has been proposed as a preferential marker of atherosclerosis susceptibility compared to leptin and adiponectin alone . We determined the extent to which the L/A ratio predicts incident cardiovascular disease ( CVD ) taking account of clinical risk factors , microalbuminuria , the total cholesterol/HDL cholesterol ( TC/HDL-C ratio ) , triglycerides , high sensitive C-reactive protein ( hs-CRP ) and insulin sensitivity ( homeostasis model assessment ( HOMA(ir ) ) ) . METHODS A community-based prospect i ve nested case-control study was carried out in 103 non-diabetic men who developed a first cardiovascular event ( cases ) and 106 male control subjects ( no clinical ly manifest CVD and no lipid lowering drug use at baseline ; median follow-up of 3.0 and 10.5 years , respectively ) .  Plasma leptin , adiponectin , the leptin/adipnectin ( L/A ) ratio , as well as hs-CRP , HOMA(ir ) and the TC/HDL-C ratio were determined at baseline . RESULTS Plasma leptin levels and the L/A ratio were higher in cases vs. controls ( p=0.002 for both ) , but the difference in adiponectin was not significant ( p=0.10 ) . Age-adjusted incident CVD was associated with plasma leptin , adiponectin and the L/A ratio ( p=0.045 to p=0.001 ) . The relationships of incident CVD with plasma leptin ( p=0.19 ) and adiponectin ( p=0.073 ) lost statistical significance after additional adjustment for smoking , waist circumference , hypertension , microalbuminuria , the TC/HDL-C ratio , hs-CRP and HOMA(ir ) . In this fully adjusted analysis , the L/A ratio remained predictive of incident CVD ( hazard ratio : 1.40 ( 95 % CI 1.05 - 1.87 ) , p=0.024 ) . CONCLUSION This study suggests that the L/A ratio may be a preferential marker of a first cardiovascular event in men compared to plasma leptin and adiponectin levels alone CONTEXT Adiponectin , a recently discovered adipocyte-derived peptide , is involved in the regulation of insulin sensitivity and lipid oxidation and , purportedly , in the development of atherosclerosis and coronary heart disease in humans . OBJECTIVE To assess prospect ively whether plasma adiponectin concentrations are associated with risk of myocardial infa rct ion ( MI ) . DESIGN , SETTING , AND PARTICIPANTS Nested case-control study among 18 225 male participants of the Health Professionals Follow-up Study aged 40 to 75 years who were free of diagnosed cardiovascular disease at the time of blood draw ( 1993 - 1995 ) . During 6 years of follow-up through January 31 , 2000 , 266 men subsequently developed nonfatal MI or fatal coronary heart disease . Using risk set sampling , controls were selected in a 2:1 ratio matched for age , date of blood draw , and smoking status ( n = 532 ) . MAIN OUTCOME MEASURE Incidence of nonfatal MI and fatal coronary heart disease by adiponectin level . RESULTS After adjustment for matched variables , participants in the highest compared with the lowest quintile of adiponectin levels had a significantly decreased risk of MI ( relative risk [ RR ] , 0.39 ; 95 % confidence interval [ CI ] , 0.23 - 0.64 ; P for trend < .001 ) . Additional adjustment for family history of MI , body mass index , alcohol consumption , physical activity , and history of diabetes and hypertension did not substantively affect this relationship ( RR , 0.41 ; 95 % CI , 0.24 - 0.70 ; P for trend < .001 ) . Further adjustment for hemoglobin A1c or C-reactive protein levels also had little impact , but additional adjustment for low- and high-density lipoprotein cholesterol levels modestly attenuated this association ( RR , 0.56 ; 95 % CI , 0.32 - 0.99 ; P for trend = .02 ) . CONCLUSIONS High plasma adiponectin concentrations are associated with lower risk of MI in men . This relationship can be only partly explained by differences in blood lipids and is independent of inflammation and glycemic status The search for complementary treatments in primary prevention of cardiovascular disease ( CVD ) is a high-priority challenge . Grape and wine polyphenol resveratrol confers CV benefits , in part by exerting anti-inflammatory effects . However , the evidence in human long-term clinical trials has yet to be established . We aim ed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD . Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded , r and omized , parallel , dose-response , placebo-controlled , 1-year follow-up trial . Patients , allocated in 3 groups , consumed placebo ( maltodextrin ) , a resveratrol-rich grape supplement ( resveratrol 8 mg ) , or a conventional grape supplement lacking resveratrol , for the first 6 months and a double dose for the next 6 months . In contrast to placebo and conventional grape supplement , the resveratrol-rich grape supplement  significantly decreased high-sensitivity C-reactive protein ( -26 % , p = 0.03 ) , tumor necrosis factor-α ( -19.8 % , p = 0.01 ) , plasminogen activator inhibitor type 1 ( -16.8 % , p = 0.03 ) , and interleukin-6/interleukin-10 ratio ( -24 % , p = 0.04 ) and increased anti-inflammatory interleukin-10 ( 19.8 % , p = 0.00 ) . Adiponectin ( 6.5 % , p = 0.07 ) and soluble intercellular adhesion molecule-1 ( -5.7 % , p = 0.06 ) tended to increase and decrease , respectively . No adverse effects were observed in any patient . In conclusion , 1-year consumption of a resveratrol-rich grape supplement  improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk ( i.e. , with diabetes or hypercholesterolemia plus ≥1 other CV risk factor ) . Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold st and ard therapy in the primary prevention of CVD We examined the effects of quercetin-rich onion peel extract supplementation on adipokine expressions from adipose tissues in a diet-induced obese animal model . Male Sprague-Dawley rats ( n = 24 ) were r and omly assigned into control ( n = 8) , high fat diet ( HF , n = 8) and high fat diet with onion peel extract ( HFOE , n = 8) . After 8 weeks , serum biochemical parameters , weights of adipose tissues ( epididymal , perirenal and mesenteric fats ) and adipokine mRNA levels ( adiponectin , IL (interleukin)-6 and visfatin ) along with PPAR ( peroxisome proliferator-activated receptor ) γ2 from adipose tissues were measured . After the 8 week supplementation , mesenteric fat weights were lower in the HFOE group than the HF group ( p < 0.05 ) . Adiponectin mRNA levels ( mesenteric fats ) were remarkably higher in the HFOE group than the other groups ( p < 0.05 for both ) . Levels of PPARγ2 mRNA ( mesenteric fats ) were significantly higher in the HF group ( p < 0.05 ) than those in the control group , but those in the HFOE group were not different from those in the control group . The IL-6 mRNA levels ( perirenal and mesenteric fats ) were higher in the HF and HFOE groups , but those in the HFOE group were slightly lower than those in the HF group . In conclusion , quercetin-rich onion peel extract supplementation  influenced adipokine expressions , particularly from mesenteric fat , addressing the modulatory effect of this substance on obesity-induced inflammation OBJECTIVE To evaluate the efficacy of an orlistat-resveratrol ( O-R ) combination in subjects with obesity over a 6-month period . METHODS This study was a double-blind , parallel , r and omized controlled clinical trial . Patients fulfilling the selection criteria ( age from 20 to 60 years and body mass index ( BMI ) ≥30 and ≤39.9 kg/m(2 ) ) consumed an energy-reduced diet with 500 fewer calories than their usual diet for 2 weeks . Then the participants were r and omly assigned to four groups , placebo , resveratrol , orlistat , or O-R , and they consumed the energy-reduced diet for 6 months . The study consisted of seven visits . During each visit , a 24-h recall was performed , along with measurements of anthropometric and serum biochemical parameters . RESULTS A total of 161 participants were selected . Of these , 84 participants completed the study . A significant weight loss of -6.82 kg ( 95 % CI -8.37 to -5.26 ) was observed in the O-R group compared with -3.50 kg ( -5.05 to -1.95 , P = 0.021 ) in the placebo group . In contrast , the -6.02 kg ( -7.68 to -4.36 ) orlistat and -4.68 kg ( -6.64 to -2.71 ) resveratrol monotherapy losses did not significantly differ from the placebo . Significant decreases in BMI , waist circumference , fat mass , triglycerides , leptin , and leptin/adiponectin ratio were observed with the O-R combination . CONCLUSIONS The O-R combination was the most effective weight loss treatment Numerous studies have shown that resveratrol ( RES ) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited . Furthermore , the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood . Therefore , the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells ( P BMC s ) associated to the one-year daily intake of a RES enriched ( 8 mg ) grape extract ( GE-RES ) in hypertensive male patients with type 2 diabetes mellitus ( T2DM ) . We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs ( miRs ) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES . We also examined the changes in several serobiochemical variables , inflammatory and fibrinolytic markers . Our results showed that supplementation with GE or GE-RES did not affect body weight , blood pressure , glucose , HbA1c or lipids , beyond the values regulated by gold st and ard medication in these patients . We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels . The expression of the pro-inflammatory cytokines CCL3 , IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in P BMC s from patients taking the GE-RES extract . Also , a group of miRs involved in the regulation of the inflammatory response : miR-21 , miR-181b , miR-663 , miR-30c2 , miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months . Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients
target: Resveratrol  significantly improves adiponectin but does not affect leptin concentrations .
background: Abstract The results of human clinical trials have revealed that the effects of resveratrol on adipokines are inconsistent .