Collagen β(1-O) galactosyltransferase 2 deficiency contributes to lipodystrophy and aggravates NAFLD related to HMW adiponectin in mice

Adiponectin is a beneficial adipocyte-secreted hormone, which circulates in a variety of multimeric forms termed low and high molecular weight (LMW/HMW). Effectiveness of clinical therapeutic trials which target adiponectin rely on accurate determination of circulating total and HMW adiponectin levels but the accuracy may be influenced by variations in sample handling processes. The aim of this pilot study was to investigate the effects of delayed processing of blood samples on the concentration of total and HMW adiponectin.Materials and Methods: Fasting blood samples were collected for analysis of total and HMW adiponectin concentrations in EDTA plasma and serum from eight healthy participants. Samples were centrifuged post 15 min storage at 4oC as the comparative ‘ideal’ method or after up to 72 h of refrigerated storage or 6 h at room temperature. Total and HMW adiponectin concentrations were measured by ELISA.Results: Under ideal handling conditions measurements of total and HMW adiponectin concentrations were significantly higher in serum than in plasma (mean difference: -1.3 µg/mL [95% CI: -1.6, -1.0], p<0.001; and, -0.6 µg/mL [95% CI: -0.7, -0.5], p<0.001, respectively). Storage of blood samples at 4oC for 72 h resulted in significant reductions in concentration of total adiponectin in serum (mean difference: -1.4 µg/mL [95% CI: -2.0, -0.8], p=0.001) and HMW adiponectin in plasma (mean difference: -0.6 µg/mL [95%CI: -0.9, -0.2], p=0.007), compared with ideal conditions. Further analysis of serum samples showed a significant decrease in total adiponectin concentration after 6 h storage at 4oC (mean difference: -1.4 µg/mL [95% CI: -2.0, -0.8], p=0.001) compared with ideal conditions.Conclusions: Delayed processing of samples may have differential effects on the concentration of total and HMW adiponectin in serum or plasma. Larger studies are warranted for clinical intervention trials.

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Effects of Oral Vitamin C Supplementation on Liver Health and Associated Parameters in Patients With Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial

Frontiers in Nutrition ◽

10.3389/fnut.2021.745609 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhangya He ◽

Xiaomin Li ◽

Hexiang Yang ◽

Pei Wu ◽

Shanshan Wang ◽

...

Keyword(s):

Liver Disease ◽

Glucose Metabolism ◽

Vitamin C ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Hmw Adiponectin ◽

Liver Health ◽

Glutamyl Transferase ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent hepatic disorder worldwide, and an unhealthy lifestyle is the leading risk factor for its occurrence. Vitamin C (VC) has been suggested to protect NAFLD, whereas evidence from randomized controlled trials (RCTs) is sparse. In this study, we aimed to investigate the potential benefits of VC supplementation daily on liver health and associated parameters in patients with NAFLD. In this double-blind, RCT, 84 patients with NAFLD, aged 18–60 years old, were assigned to 12 weeks of oral treatment with either low (250 mg/day, n = 26), medium (1,000 mg/day, n = 30), or high (2,000 mg/day, n = 28) doses of VC supplements. After the intervention, the Medium group had a more significant decrease in aspartate aminotransferase [Medium, −5.00 (−10.25, −1.75) vs. High, −2.50 (−7.75, 0.00), P = 0.02] and alanine aminotransferase [Medium, −8.00 (−18.00, −1.75) vs. High, −3.50 (−13.75, 4.25), P = 0.05; Medium vs. Low, −3.00 (−9.00, 5.50), P = 0.031]. The levels of other indicators of liver health, such as gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, and direct bilirubin were decreased after the intervention but comparable among the three groups and so did the parameters of glucose metabolism, such as fasting insulin, fasting glucose, and homeostasis model assessment for insulin resistance. The plasma level of VC in patients and total adiponectin and high molecular weight (HMW) adiponectin levels were also elevated but not in a dose-dependent manner. Meanwhile, analysis of fecal microbiota composition showed an increase in the alpha diversity (Abundance-based Coverage Estimator (ACE), Shannon, chao1, and Simpson) both in the Low and the Medium groups. A total of 12 weeks of VC supplementation, especially 1,000 mg/day, improved liver health and glucose metabolism in patients with NAFLD. The elevated plasma levels of VC, total and HMW adiponectin, and the improvement of intestinal microbiota may have made some contributions.

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Total and HMW Adiponectin is Independently Associated with B-type Natriuretic Peptide and Anemia in Chronic Hemodialysis Patients

Internal Medicine ◽

10.2169/internalmedicine.51.8636 ◽

2012 ◽

Vol 51 (23) ◽

pp. 3247-3252 ◽

Cited By ~ 4

Author(s):

Yasuhiro Abe ◽

Tomoji Matsumae ◽

Satoshi Eto ◽

Maho Watanabe ◽

Kenji Ito ◽

...

Keyword(s):

Natriuretic Peptide ◽

Hemodialysis Patients ◽

Chronic Hemodialysis ◽

Hmw Adiponectin

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Large-for-Gestational-Age, Leptin, and Adiponectin in Infancy

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab642 ◽

2021 ◽

Author(s):

Rong Huang ◽

Yu Dong ◽

Emile Levy ◽

Pierre Julien ◽

Isabelle Marc ◽

...

Keyword(s):

Gestational Age ◽

Skinfold Thickness ◽

Large For Gestational Age ◽

Z Score ◽

White Ethnicity ◽

Female Sex ◽

Hmw Adiponectin ◽

Gestational Age At Delivery ◽

Score Gain

Abstract Context Fetal overgrowth “programs” an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health. Objective This work aimed to evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants. Methods In the Canadian 3D birth cohort, we studied 70 LGA (birth weight > 90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) infants matched by maternal ethnicity, smoking, and gestational age at delivery. The primary outcomes were fasting leptin, and total and high-molecular-weight (HMW) adiponectin concentrations at age 2 years. Results LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, and total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0 to 24 months, current BMI, and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and White ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0 to 24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only. Conclusion This study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weight gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA individuals.

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Linoleic Acid–Rich Oil Supplementation Increases Total and High-Molecular-Weight Adiponectin and Alters Plasma Oxylipins in Postmenopausal Women with Metabolic Syndrome

Current Developments in Nutrition ◽

10.1093/cdn/nzaa136 ◽

2020 ◽

Vol 4 (9) ◽

Author(s):

Rachel M Cole ◽

Sarah Puchala ◽

Jia-Yu Ke ◽

Mahmoud Abdel-Rasoul ◽

Kristin Harlow ◽

...

Keyword(s):

Metabolic Syndrome ◽

Molecular Weight ◽

Linoleic Acid ◽

High Molecular Weight ◽

Oil Consumption ◽

Open Label ◽

High Molecular Weight Adiponectin ◽

Markers Of Inflammation ◽

Hmw Adiponectin ◽

Total Adiponectin

ABSTRACT Background The onset of menopause increases the risk of metabolic syndrome (MetS). Adiponectin is an adipokine associated with insulin sensitivity that is lower in people with MetS. Supplementing diets with linoleic acid (LA)-rich oil increased adiponectin concentrations and improved glucose control in women with type 2 diabetes. The effect of LA on adipokines, especially total and the bioactive form of adiponectin, high-molecular-weight (HMW) adiponectin, in women with MetS is unknown. Objectives The aim of this study was to explore the effect of supplementation of the diet with an oil rich in LA on adipokines in women with MetS. The effect of the LA-rich oil (LA-oil) on oxylipins, key metabolites that may influence inflammation and metabolism, was also explored. Methods In this open-label single-arm pilot study, 18 postmenopausal nondiabetic women with MetS enrolled in a 2-phase study were instructed to consume LA-rich vegetable oil (10 mL/d) as part of their habitual diets. Women consumed an oleic acid–rich oil (OA-oil) for 4 wk followed by an LA-oil for 16 wk. Fasting concentrations of adipokines, fatty acids, oxylipins, and markers of glycemia and inflammation were measured. Results After 4 wk of OA-oil consumption, fasting glucose and total adiponectin concentrations decreased whereas fasting C-reactive protein increased. After 16 wk of LA-oil supplementation total and HMW adiponectin and plasma oxylipins increased. Markers of inflammation and glycemia were unchanged after LA-oil consumption. Conclusions Supplementation with LA-oil increased total and HMW adiponectin concentrations and altered plasma oxylipin profiles. Larger studies are needed to elucidate the links between these changes and MetS. This trial was registered at clinicaltrials.gov as NCT02063165.

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Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy295 ◽

2019 ◽

Vol 109 (3) ◽

pp. 635-647 ◽

Cited By ~ 17

Author(s):

Dong Hang ◽

Ane Sørlie Kværner ◽

Wenjie Ma ◽

Yang Hu ◽

Fred K Tabung ◽

...

Keyword(s):

Health Professionals ◽

Coffee Consumption ◽

Blood Draw ◽

Plasma Biomarkers ◽

Inflammatory Pathways ◽

Hmw Adiponectin ◽

Total Adiponectin ◽

Decaffeinated Coffee ◽

Free Estradiol ◽

Igfbp 3

ABSTRACT Background Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood. Objectives The aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases. Methods We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone–binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses’ Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors. Results Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (−8.7%), IGFBP-3 (−2.2%), estrone (−6.4%), total estradiol (−5.7%), free estradiol (−8.1%), leptin (−6.4%), CRP (−16.6%), IL-6 (−8.1%), and sTNFR-2 (−5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee. Conclusion Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.

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A method comparison of total and HMW adiponectin: HMW/total adiponectin ratio varies versus total adiponectin, independent of clinical condition

Clinica Chimica Acta ◽

10.1016/j.cca.2016.12.009 ◽

2017 ◽

Vol 465 ◽

pp. 30-33 ◽

Cited By ~ 8

Author(s):

Merel van Andel ◽

Madeleine L. Drent ◽

Antonius E. van Herwaarden ◽

Mariëtte T. Ackermans ◽

Annemieke C. Heijboer

Keyword(s):

Clinical Condition ◽

Method Comparison ◽

Hmw Adiponectin ◽

Total Adiponectin

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Association of the +45T>G and +276G>T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women

Acta Endocrinologica ◽

10.1530/eje-09-0492 ◽

2009 ◽

Vol 161 (6) ◽

pp. 845-852 ◽

Cited By ~ 53

Author(s):

Labros Melistas ◽

Christos S Mantzoros ◽

Meropi Kontogianni ◽

Smaragdi Antonopoulou ◽

Jose M Ordovas ◽

...

Keyword(s):

Insulin Resistance ◽

Body Composition ◽

Plasma Lipid ◽

Snp Analysis ◽

Model Assessment ◽

Adiponectin Gene ◽

Lipid Levels ◽

Female Population ◽

Insulin Levels ◽

Hmw Adiponectin

ObjectiveWe explored potential associations of two single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ; +45T>G, rs2241766 and +276G>T, rs1501299) with circulating total and high-molecular weight (HMW) adiponectin, insulin resistance (IR), and markers of obesity in a healthy Greek female population.Design and methodsThe two SNPs were genotyped in 349 women without diabetes (mean age: 47.0±12.1 years, mean body mass index: 28.9±5.6 kg/m2). Total and HMW adiponectin concentrations, body composition variables, IR parameters, and plasma lipid levels were determined.ResultsIn single SNP analysis adjusting for several potential confounders, SNP +276G>T was associated with higher fasting insulin levels (P=0.01) and higher homeostasis model assessment index for IR (HOMA-IR; P=0.009), and SNP +45T>G was associated with lower insulin levels and HOMA-IR (P=0.05 and P=0.07 respectively). No association with total or HMW adiponectin, plasma lipid levels, and body composition variables was observed; however, haplotype analysis revealed that subjects homozygous for the most common +45T/+276G haplotype had lower total adiponectin levels than did noncarriers of this haplotype (P=0.02). The observed differences in HOMA-IR were very significant among women with a higher body fat (BF) percentage (≥ the population median of 41%; all P≤0.005), but not among leaner individuals (P for interactions 0.01–0.07), thus suggesting that ADIPOQ effects on insulin sensitivity may depend upon BF status.ConclusionOur data suggest a significant role of ADIPOQ variants at positions +45 and +276 in the development of IR in healthy Greek women possibly through an interaction with BF.

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Altered body composition and energy expenditure but normal glucose tolerance among humans with a long-chain fatty acid oxidation disorder

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00225.2013 ◽

2013 ◽

Vol 305 (10) ◽

pp. E1299-E1308 ◽

Cited By ~ 16

Author(s):

Melanie B. Gillingham ◽

Cary O. Harding ◽

Dale A. Schoeller ◽

Dietrich Matern ◽

Jonathan Q. Purnell

Keyword(s):

Insulin Resistance ◽

Energy Expenditure ◽

Glucose Tolerance ◽

Normal Glucose Tolerance ◽

Total Energy Expenditure ◽

Acid Oxidation ◽

Hmw Adiponectin ◽

Normal Glucose ◽

Lchad Deficiency ◽

Long Chain

The development of insulin resistance has been associated with impaired mitochondrial fatty acid oxidation (FAO), but the exact relationship between FAO capacity and glucose metabolism continues to be debated. To address this controversy, patients with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) deficiency underwent an oral glucose tolerance test (OGTT) and measurement of energy expenditure, body composition, and plasma metabolites. Compared with controls, patients with LCHAD deficiency had a trend toward higher total body fat and extramyocellular lipid deposition but similar levels of intramyocelluar and intrahepatic lipids. Resting energy expenditure was similar between the groups, but respiratory quotient was higher and total energy expenditure was lower in LCHAD-deficient patients compared with controls. High-molecular-weight (HMW) adiponectin levels were lower and plasma long-chain acylcarnitines were higher among LCHAD-deficient patients. Fasting and post-OGTT levels of glucose, insulin, and ghrelin, along with estimates of insulin sensitivity, were the same between the groups. Despite decreased capacity for FAO, lower total energy expenditure and plasma HMW adiponectin, and increased plasma acylcarnitines, LCHAD-deficient patients exhibited normal glucose tolerance. These data suggest that inhibition of the FAO pathway in humans is not sufficient to induce insulin resistance.

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