META060 from hops reduces weight gain, increases weight loss, improves fasting glucose and insulin sensitivity in high‐fat fed mice
Veera Reddy KondaIrene O.C.M. VroegrijkJanna A. van DiepenGary DarlandAnuradha DesaiJohn G. BabishMatthew L. TrippJeffrey S. BlandPeter J. Voshol
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Abstract:
Obesity is a complex disease resulting from a prolonged positive imbalance between energy intake and energy expenditure with excess fat accumulating in various organs and tissues. META060, a defined hop extract, was analyzed in various cell models of obesity/type‐2 diabetes. META060 stimulated the secretion of GLP‐1 in intestinal L cells (NCI‐H716); stimulated the production of adiponectin in adipocytes (3T3‐L1); activated the phosphorylation of AMPK levels in muscle cells (C2C12); and inhibited nitric oxide levels in both myocytes and macrophages (RAW264.7). META060 was evaluated in a mouse model of high fat diet (HFD) induced obesity. Mice supplemented for 14 weeks with META060 (100 mg/kg body weight) prevented the HFD induced weight gain, and the rate of weight gain was similar to that of the low fat diet group. META060 significantly reduced HFD induced fat accumulation in viscera, subcutaneous tissues and gonads, and exhibited a significant reduction in fasting glucose and insulin. In addition, mice switching to HFD+META060 after 14 weeks of HFD dramatically increased the weight loss within 2 weeks. In oral glucose tolerance test, addition of META060 to HFD for 14 weeks reduced insulin levels. In conclusion, META060 reduced weight gain, fasting plasma insulin and glucose levels, and improved insulin sensitivity in mice fed with high fat diet. Supported by MetaProteomics, LLC.Keywords:
Diet-induced obese
This chapter contains sections titled: Introduction Adiponectin Structure and Post-Translational Modifications Significance and Bioactivity of Adiponectin Multimers Adiponectin and Liver Adiponectin and Skeletal Muscle Adiponectin and the Vasculature Adiponectin and the Brain Adiponectin Expression and Secretion Adiponectin Secretion Ectopic Adiponectin Expression Regulation of Expression and Secretion Adiponectin Clearance Adiponectin Receptors and Downstream Effectors Adiponectin Signaling Conclusions References
Adiponectin receptor 1
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Objective To study the effect of high-fat diet(HFD) on the expression of adiponectin mRNA,the level of serum adiponectin,and the proper mechanism of different susceptibility to obesity.Method Eighty male Sprague-Dawley(SD) rats were randomly divided into control group(n=10) and high-fat group(n=70),and fed normal and HFD respectively for 12 w.HFD group was subdivided into obesity(DIO) and obesity-resistant rats(DIO-R) according to body weight,and fed HFD continuously for another 8w.The body weight and food intake were recorded.Wet weight of fat pad and the ratio of fat to body weight were measured at the end of experiment.Adiponectin mRNA in adipose tissue was detected by real time PCR,and serum adiponectin was detected by ELISA.Results The body weights,body fat percent,caloric intake,energy efficiency in DIO rats were higher significantly than those in DIO-R rats,but adiponectin mRNA and serum adiponectin in DIO rats were lower than those in DIO-R rats.Conclusion The adiponectin mRNA expression in adipose tissae and serum adiponectin concentration were decreased in the rats fed high-fat diet and might be closely associated with the development of different susceptibility to obesity.
Diet-induced obese
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Adipose tissue has been identified as an endocrine organ secreting adipokines involved in metabolic and inflammatory pathways. Adiponectin, an anti-inflammatory adipokine, is reduced in sepsis. High Molecular Weight (HMW) adiponectin, the biologically most relevant molecule, has been investigated very little in human sepsis. Zinc-alpha2-glycoprotein (ZAG) is a novel adipokine and its expression in adipose tissue is positively correlated with adiponectin expression. It is not yet known whether ZAG has a role in sepsis. In this study we assessed levels of HMW adiponectin and ZAG during different stages of sepsis. A prospective observational pilot study was carried out on 21 septic patients. Serum samples were taken on day 1 and 2 post ICU admission and on day of discharge. Samples were analysed for total and HMW adiponectin, HMW/total adiponectin ratio, and ZAG. Results were correlated with clinical and metabolic data. There were no differences in total adiponectin, HMW adiponectin and ZAG plasma concentrations between day 1 (admission) and day 2 of the sepsis episode. Compared to admission, a significant increase in total and HMW adiponectin and ZAG was observed on the day of discharge when clinical improvement had been achieved. There was also an increase in the HMW/total adiponectin ratio at that time. Our data demonstrate an increase in both HMW adiponectin and total adiponectin in patients who had clinically recovered from sepsis. The increase in HMW/total adiponectin ratio with improvement of the clinical condition suggests that HMW adiponectin may have a greater role in the inflammatory process and insulin resistance seen in sepsis. In this pilot study, we have also demonstrated a significant increase in ZAG in critically ill patients temporally related to recovery from sepsis.
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Summary Objective This study is the first to report high molecular weight (HMW) adiponectin in newborns from normal and pre‐eclamptic pregnancies (PE). Adiponectin is adversely related to Metabolic Syndrome‐linked diseases such as obesity, dyslipidaemia, insulin resistance and hypertension. It is abundant in human plasma where it circulates as several characteristic multimeric forms of which the HMW form is the most active. As children from PE‐pregnancies have a greater susceptibility to hypertensive disorders later in life, we hypothesized that adiponectin measured in cord blood could be a putative risk marker. Design and patients Cross‐sectional, hospital‐based study of newborns from mothers with pre‐eclampsia (30 cases and 62 controls). Venous cord blood samples were collected immediately after birth and were analysed for total adiponectin and HMW adiponectin. Measurements Total adiponectin and HMW adiponectin were measured by commercially available enzyme‐linked immunosorbent assay (ELISA) kits. Results The PE newborns showed a significantly lower gestational age (GA), total adiponectin and HMW adiponectin levels than the controls. No differences in adiponectin levels were found between case and control groups when correcting for GA. In combined groups, log (total adipo) = 0·40 + 0·027*GA; r = 0·43, P < 0·001. Furthermore, the HMW form is the dominant form of adiponectin: HMW adipo = –5·06 + 0·81*total adipo; r = 0·90, P < 0·001. Conclusions Adiponectin in cord blood from PE pregnancies may not be a tentative risk marker for Metabolic Syndrome‐linked diseases. HMW adiponectin is the dominant form of adiponectin in cord blood. Its role during pregnancy and postnatal life should be further explored.
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Abstract Aims: To study circulating levels and distribution of adiponectin multimers [low molecular weight (LMW)-, medium molecular weight (MMW)- and high molecular weight (HMW)-adiponectin] in preterm and full-term infants. Methods: Total serum adiponectin and its multimers were measured in 40 healthy infants at the age of one month and associations with anthropometric parameters [body weight and length, body mass index (BMI)], weight gain and metabolic indices (glucose, insulin) were examined. Twenty of the infants were born preterm (gestational age 33.2±1.6 weeks). Results: LMW-adiponectin level and its fractional ratio to total adiponectin were significantly higher in full-term than in preterm infants (P<0.001 and P<0.01, respectively), whereas, MMW-adiponectin level and its ratio were significantly lower (P=0.03 and P=0.01, respectively). HMW-adiponectin did not differ significantly between full-term and preterm infants and accounted for almost 60% of total adiponectin levels in both groups. HMW-adiponectin, but not MMW adiponectin or LMW adiponectin, correlated significantly with anthropometric measurements, similarly to total adiponectin; in addition, HMW adiponectin correlated significantly with weight gain. Conclusions: HMW adiponectin is the most prevalent form in infants. Circulating levels and distribution of MMW- and LMW-adiponectin differ between full-term and preterm infants, but the role of these adiponectin multimers needs to be studied further.
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In many studies, high-molecular-weight (HMW) adiponectin has been considered the active form of adiponectin. However, whether HMW adiponectin is a good surrogate marker for coronary artery disease still needs to be elucidated.We conducted a hospital-based cross-sectional study to examine the relationship between total, HMW or non-HMW adiponectin concentrations and coronary stenosis in 83 male patients and 138 male controls.Patients with coronary stenosis had significantly lower total adiponectin concentrations compared with controls. Non-HMW adiponectin concentrations in cases were significantly lower than the controls. However, there were no significant differences between cases and controls in HMW adiponectin concentrations. From the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) for total and non-HMW adiponectin was significantly larger than that for HMW adiponectin concentrations. Of the three models, that for non-HMW adiponectin showed the largest AUC (total adiponectin 0.74, HMW adiponectin 0.54, and non-HMW adiponectin 0.79).Despite associations between total adiponectin levels and coronary stenosis, our data go against any apparent association between HMW adiponectin concentrations and coronary stenosis.
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An important link between adiponectin and hypertension has been proposed in clinical studies. In the circulation, adiponectin is predominantly present in multimeric complexes, of which high–molecular weight (HMW) adiponectin is thought to represent the biological active form. The authors investigated which role the different multimeric adiponectin isoforms play in context with hypertension as compared to total adiponectin levels. Fifty (19 normotensive/31 hypertensive) patients were included in the study. Total adiponectin and adiponectin multimers were determined by enzyme‐linked immunosorbent assay and western blot. The authors analyzed associations between adiponectin multimer levels and blood pressure. Total adiponectin concentrations were not significantly different between hypertensive and normotensive patients (6.8±2.3 vs 7.5±4.2 μg/mL). HMW adiponectin was significantly lower (P< .05) and low–molecular weight adiponectin was significantly higher ( P< .01) in hypertensive than in normotensive persons (3.8±1.7 vs 5.2±3.0 μg/mL and 0.9±0.5 vs 1.8±0.9, respectively). Low molecular weight was an independent predictor for the presence of hypertension (effect coefficient: 0.160–0.445; P< .001) in multivariate analyses. These results suggest that the composition of the molecular weight forms of adiponectin in hypertension are characterized by reduced HMW adiponectin, the proposed major active form of adiponectin, and increased low–molecular weight adiponectin. Moreover, the latter represents an independent predictor of prevalent hypertension, suggesting an association between adiponectin multimer composition and hypertension.
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Adiponectin is one of the adipocytokines that is derived from adipose tissue.It has anti-inflammatory,anti-diabetic,anti—atherogenic and insulin-sensitizing effects.Recent researches show Adiponectin is relational with chronic liver disease,In text,we describe adiponectin,source,adiponectin,structure,adiponectin,biological function and effect of adiponectin in chronic liver disease.
Chronic liver disease
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Objective To study the pathogenesis in type 2 diabetes(DM) retinopathy(DR)about adiponectin and tumor necrosis factor(TNF-α).Method Adiponectin and TNF-α were measured in the serum of 90 cases of type 2 diabetes patients and 40 healthy human by enzyme-linked immunosorbent assay(ELISA).The 90 patients were divided into non-DR(NDR) group,background-DR group(BDR) and proliferative-DR(PDR) grioup.Result ①The serum adiponectin and TNF-α levels in DM group were lower than in the control group(P0.05);② The levels of adiponectin and TNF-α in BDR group were less than in NDR group(P0.05);③The contents of adiponectin and TNF-α in PDR group were less than NDR group's(P0.01);④The contents of adiponectin and TNF-α in PDR group were less than BDR group(P0.05);⑤The gravity of DR were negatively correlated to the levels of adiponectin(r=-0.428,P0.01).Conclusion The reduction of adiponectin and TNF-α plays an important role in the pathogenesis of DM.The adiponectin and TNF-α may be involved in the occurrence and development of DR because the levels of blood adiponectin and TNF-α are more lower in type 2 diabetic retinopathy.
Pathogenesis
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