Increase In High Molecular Weight Adiponectin Research Articles

Effects of Febuxostat Therapy on Circulating Adipokine Profiles in Patients with Overweight or Obesity and Asymptomatic Hyperuricemia: A Randomized Controlled Study.

Elevated levels of serum uric acid (SUA) are strongly associated with several components of the metabolic syndrome, particularly obesity. Previous studies have reported the correlation between SUA levels, xanthine oxidoreductase (XOR) activity, and the imbalanced adipokine levels that are characteristic of obesity. In this study, we explored the effect of febuxostat on circulating adipokine profiles in patients with overweight or obesity and asymptomatic hyperuricemia. This study was a single-center, randomized, and controlled clinical trial that enrolled 130 participants with asymptomatic hyperuricemia and obesity. One hundred seventeen participants were included in the final analysis, with 60 participants in the febuxostat group and 57 in the control group. We compared the circulating adipokine levels at 3 and 6 months, including high molecular weight (HMW) adiponectin, chemerin, omentin, monocyte chemotactic protein-1, asprosin, fibroblast growth factor 21, neuregulin-4, leptin, resistin, vaspin, visfatin, adipsin, and assessed the correlation between changes in adipokine levels (Δadipokines) and changes in XOR activity (ΔXOR) after febuxostat treatment. The results showed that an increase in HMW adiponectin and omentin levels and a decrease in chemerin and asprosin levels at 3 or 6 months compared to the control group. Additionally, a positive correlation was observed between ΔXOR activity and Δasprosin. Furthermore, after adjusting for triglyceride (ΔTG) and serum uric acid (ΔSUA) in multiple linear regression analyses, we found that ΔXOR activity was independently correlated with Δasprosin. This study may provide important evidence that febuxostat could alleviate the imbalance in circulating adipokine levels in patients with overweight or obesity and asymptomatic hyperuricemia. Furthermore, we observed a positive correlation between changes in asprosin levels and changes in XOR activity after febuxostat treatment.

Effects of weight-loss on adipokines, total and regional body composition and markers of metabolic syndrome in women who are overweight and obese

Obesity among aging women is associated with increased risk for metabolic and cardiovascular diseases. Weight-loss has been shown to reduce disease risk; however, it remains unclear how changes in adipokines following weight-loss are associated with markers of metabolic and cardiovascular health in women. The aim of this study was to determine the effects of a 3-month intensive lifestyle management-focused weight-loss program on the interactions between adipokines, total and regional body composition, and biomarkers of cardiovascular and metabolic health. Women who were overweight or obese (n = 43, age = 49.2 ± 1.5 years, body mass index (BMI) = 34.5 ± 0.9 kg/m2; waist circumference (WC) = 99.8 ± 2.2 cm) completed a 3-month weight-loss program consisting of a reduced energy intake to 1200–1500 kcals/day combined with a progressive walking program targeting 300 min/wk. At 3-months, average body mass was reduced 8.3 % (ΔBMI −8.0 %; ΔWC −6.6 %). Weight-loss lowered fasting glucose (−12.1 %), insulin (−23.2 %), total cholesterol (−11.0 %), and LDL-C (−12.2 %) concentrations, and HOMA-IR (−32.4 %). Leptin was decreased 32.6 %, high molecular weight (HMW) adiponectin increased 25.0 %, and adiponectin:leptin ratio increased 1.27-fold. The change in fat mass was positively correlated with Δleptin (r = 0.527) and inversely correlated with Δadiponectin:leptin ratio (r = −0.547). The ΔHMW adiponectin inversely correlated with Δinsulin (r = −0.360) and ΔHOMA-IR (r = −0.304), and ΔLDL-C (r = −0.305), whereas Δleptin correlated with Δtriglyceride (r = 0.366) and Δtotal cholesterol (r = 0.402). Weight-loss in women who were overweight and obese was associated with a reduction in leptin and increase in HMW adiponectin and adiponectin:leptin ratio. Correlations revealed that changes in these adipokines were uniquely associated with improvements in select markers of metabolic and cardiovascular disease risk.

Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY.

The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated that glycemic failure rates in the three treatments combined-metformin plus rosiglitazone, metformin alone, and metformin plus lifestyle-were higher in non-Hispanic blacks (NHB; 52.8%) versus non-Hispanic whites (NHW; 36.6%) and Hispanics (H; 45.0%). Moreover, metformin alone was less effective in NHB versus NHW versus H youth. This study describes treatment-associated changes in adiponectin, insulin sensitivity, and β-cell function over time among the three racial/ethnic groups to understand potential mechanism(s) responsible for this racial/ethnic disparity. TODAY participants underwent periodic oral glucose tolerance tests to determine insulin sensitivity, C-peptide index, and oral disposition index (oDI), with measurements of total and high-molecular-weight adiponectin (HMWA). At baseline NHB had significantly lower HMWA than NHW and H and exhibited a significantly smaller increase (17.3% vs. 33.7% vs. 29.9%, respectively) during the first 6 months overall. Increases in HMWA were associated with reductions in glycemic failure in the three racial/ethnic groups combined (hazard ratio 0.61, P < 0.0001) and in each race/ethnicity separately. Over time, HMWA was significantly lower in those who failed versus did not fail treatment, irrespective of race/ethnicity. There were no differences in treatment-associated temporal changes in insulin sensitivity, C-peptide index, and oDI among the three racial/ethnic groups. HMWA is a reliable biomarker of treatment response in youth with type 2 diabetes. The diminutive treatment-associated increase in HMWA in NHB (∼50% lower) compared with NHW and H may explain the observed racial/ethnic disparity with higher therapeutic failure rates in NHB in TODAY.

Objectively Measured Physical Activity Is Negatively Associated with Plasma Adiponectin Levels in Minority Female Youth

Objective. To evaluate the relationship between adiponectin and physical activity (PA) in minority female youth. Methods. Plasma adiponectin was measured in 39 females (mean age 9.2 ± 0.9 years; 30 Latina, 9 African-American; 56% overweight). PA was assessed by accelerometry. Mean minutes per day spent in daily PA (DPA) (≥3 metabolic equivalents (METs)), moderate PA (MPA)(4–7 METs), vigorous PA (VPA)(≥7 METs), and moderate-to-vigorous PA (MVPA)(≥4 METs) were calculated. The association between adiponectin and PA, controlling for age, fat weight, lean weight, and insulin sensitivity (SI) was analyzed using linear regression. Results. Adiponectin correlated with fat weight (r = −0.43, P < .01) and SI (r = 0.52, P < .01). Minutes spent in DPA (β = −0.40, P = .02), MPA (β = −0.36, P = .04), or MVPA (β = −0.37, P = .03) were predictors of adiponectin in the adjusted model. Conclusions. Higher PA levels were related to lower adiponectin levels. Potential mechanisms include upregulation of adiponectin receptors or an increase in high-molecular weight adiponectin with increasing PA.

A lack of increase in high molecular weight-adiponectin in macroalbuminuric subjects with metabolic syndrome may exert renal and atherosclerotic risks

We assessed serum levels of total- and HMW-adiponectin as well as carotid intima–media thickness (IMT) in relation to the levels of albuminuria in subjects with and without metabolic syndrome (MS). Consecutive 291 subjects were enrolled in this study. Waist circumference (WC) was measured and MS was diagnosed according to the Japanese criteria. Urinary albumin/creatinine ratio (ACR) was determined, and then divided into three stages; normo-, micro- and macroalbuminuria. Of all subjects, 95 were defined as having MS (MS+) and the other 196 were not (MS−). There was no significant difference in age between MS+ and MS− groups. The prevalence of micro- and macroalbuminuria was about twice as high in the MS+ than in the MS−. Although there was no difference in the WC among normo-, micro- and macroalbuminuric subjects in both MS+ and MS−, serum HMW-adiponectin levels and the HMW/total-adiponectin ratio in the macroalbuminuric MS− were significantly higher than that in the normo- and microalbuminuric MS−. However, these parameters did not change with an increase in urinary ACR among MS+. IMT was greatest in macroalbuminuric MS+ when compared with other groups. Multiple regression analysis revealed that HMW/total-adiponectin ratio is associated with urinary ACR independent of age, gender and presence of MS. We concluded that increased serum HMW-adiponectin by unknown mechanisms, at abstract least independent of WC, might help protect against renal and atherosclerosis risks in macroalbuminuric MS−.

Preferential increase in high-molecular weight adiponectin after niacin

Objective Recently we have demonstrated that treatment with niacin raises adiponectin between 52% and 95% in patients with the metabolic syndrome. In this study we investigated whether all three adiponectin fractions are increased equally, and, secondly, whether the increase in the biologically most active high-molecular weight (HMW) fraction can prevent the deterioration of insulin sensitivity that was also observed after niacin. Methods and results We used sera frozen at −80 °C from a randomized double-blind placebo-controlled treatment study in which 20 men with the metabolic syndrome received 1500 mg niacin for 6 weeks. Low- and medium-molecular weight adiponectin increased by 35% and 33%, respectively, but HMW adiponectin by 88% (all p < 0.05). The increase in HMW adiponectin was almost two times as large in patients with lower BMI and better insulin sensitivity. However, treatment with niacin induced a deterioration of insulin sensitivity, as assessed by the HOMA-IR, independently of the increase in HMW adiponectin. Conclusion HMW adiponectin is the fraction most affected by treatment with niacin. The niacin-associated deterioration of insulin sensitivity, however, occurs even in subgroups with the greatest increase of HMW adiponectin.