Serum protein binding and the role of increased alpha 1‐acid glycoprotein in moderately obese male subjects.

Benedek, I. H.; Blouin, RA; McNamara, PJ

doi:10.1111/j.1365-2125.1984.tb02567.x

Cited by 80 publications

(57 citation statements)

References 16 publications

(22 reference statements)

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“…Circulating ORM levels in our study group were more than twice the average levels reported in healthy people (Fournier et al, 2000). A previous study involving morbidly obese females and moderately obese males also showed that ORM protein concentrations were doubled compared to lean controls (Benedek et al, 1983;1984). We also showed previously that serum ORM levels were significantly elevated in obese people as compared to healthy people (Lee et al, 2010).…”

Section: Discussionsupporting

confidence: 74%

Orosomucoid Serum Concentrations and Fat Depot-Specific mRNA and Protein Expression in Humans

Alfadda

Fatma

Chishti

et al. 2012

Molecules and Cells

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Obesity is associated with chronic low-grade inflammation, which contributes to systemic metabolic irregularities and obesity-linked metabolic disorders. Orosomucoid (ORM), an acute phase reactant protein, was shown to be produced in response to metabolic and inflammatory signals in the adipose tissue of obese mice, which protects them from severe inflammation and subsequent metabolic dysfunction. In this study, we examined whether there are sitespecific differences between visceral and subcutaneous adipose tissue (VAT and SAT, respectively) ORM gene and protein expression from individuals with a wide range of obesity and the relationship between expressed and circulating ORM levels and measures of adiposity, insulin resistance, and pro-and anti-inflammatory markers and adipokines. The level of circulating ORM correlated positively with BMI, body fat mass, and serum leptin. It also correlated with fasting insulin, HOMA-IR values and C-reactive protein in men. There were no site-specific differences in ORM mRNA and protein expression between VAT and SAT, nor did we find a relationship between circulating ORM levels and its mRNA expression in either fat depot. We found that ORM mRNA expression correlated with mRNA expression of TNF-α, IL-6, and adiponectin in VAT, and with TNF-α and adiponectin in SAT. These observations are the first description linking adipose tissue ORM and pro-and anti-inflammatory molecules in humans. The close links of ORM and measures of adiposity, insulin resistance, and adipose tissue inflammation in humans reinforce previous experimental data and warrant further studies to explore a possible role of ORM in the pathogenesis of obesity-associated metabolic derangements.

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Section: Discussionsupporting

confidence: 74%

Orosomucoid Serum Concentrations and Fat Depot-Specific mRNA and Protein Expression in Humans

Alfadda

Fatma

Chishti

et al. 2012

Molecules and Cells

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“…In the ATV/RTV group, female participants had a higher median BMI than the male participants, and both participants with BMI >40 were female. In this analysis, RTV protein binding was shown to be sensitive to BMI, but not ATV or EFV; in the PK literature, the relationship between obesity and protein binding has not been clearly delineated, although it is postulated that alpha‐1 acid glycoprotein concentrations, to which RTV binds, are increased in obesity 43, 44, 45. This may also be a function of sex differences, as BMI and sex are linked, and our sample size is moderate.…”

Section: Discussionmentioning

confidence: 83%

Population Pharmacokinetics Modeling of Unbound Efavirenz, Atazanavir, and Ritonavir in HIV‐Infected Subjects With Aging Biomarkers

Dumond

Chen

Cottrell

et al. 2016

CPT Pharmacom & Syst Pharma

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Unbound drug is the pharmacodynamically relevant concentration. This study aimed to determine if chronologic age or markers of biologic aging, such as the frailty phenotype and p16INK4a gene expression, altered unbound pharmacokinetics (PKs) of efavirenz (EFV) and atazanavir/ritonavir (ATV/RTV). Sixty human immunodeficiency virus (HIV)‐infected participants receiving EFV and 31 receiving ATV/RTV provided 1 to 11 samples to quantify total and unbound plasma concentrations. Population PK models with total and unbound concentrations simultaneously described are developed for each drug. The unbound fractions for EFV, ATV, and RTV are 0.65%, 5.67%, and 0.63%, respectively. Covariate analysis suggests RTV unbound PK is sensitive to body size; unbound fraction of RTV is 34% lower with body mass index (BMI) above 30 kg/m2. No alterations in drug clearance or unbound fraction with age, frailty, or p16INK4a expression were observed. Assessing functional and physiologic aging markers to inform potential PK changes is necessary to determine if drug/dosing changes are warranted in the aging population.

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“…Indeed, other inflammation markers such alpha 1 acid glycoprotein (AAG) and alpha 1 antitrypsin (AAT) have been found to be increased in obesity. [9][10][11] We therefore assessed the relationships between several circulating acute phase proteins, that is, CRP, AAG, fibrinogen (Fg) and AAT levels and both circulating and adipose tissue leptin, IL-6, TNFa and plasminogen activator inhibitor (PAI)-1 content in obese women.…”

Section: Introductionmentioning

confidence: 99%

Systemic low-grade inflammation is related to both circulating and adipose tissue TNFα, leptin and IL-6 levels in obese women

et al. 2004

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OBJECTIVE:We assessed the relationships between four circulating acute phase proteins and the circulating and adipose tissue levels of three adipocytokines. SUBJECTS: In all, 15 nondiabetic obese women with a body mass index (BMI) above 32 kg/m 2 were investigated. METHOD: Circulating concentrations of C-reactive protein (CRP), alpha 1 acid glycoprotein (AAG), fibrinogen, alpha 1 antitrypsin and both circulating and adipose tissue levels of interleukin (IL)-6, tumor necrosis factor (TNF)a and leptin were measured by either nephelometry or enzyme-linked immunosorbent assay. RESULTS: We found a strong positive correlation between both circulating and adipose tissue levels of IL-6, TNFa and leptin and serum CRP levels. All these adipose tissue adipocytokines were also positively correlated with serum AAG levels. These correlations disappeared when adjusted for fat mass, suggesting that the relationship observed was dependent on fat amount. CONCLUSION: Our results indicate a strong relationship between adipocytokines and inflammatory markers, and suggest that cytokines secreted by adipose tissue in obese subjects could play a role in increased inflammatory proteins secretion by the liver.

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Serum protein binding and the role of increased alpha 1‐acid glycoprotein in moderately obese male subjects.

Cited by 80 publications

References 16 publications

Orosomucoid Serum Concentrations and Fat Depot-Specific mRNA and Protein Expression in Humans

Orosomucoid Serum Concentrations and Fat Depot-Specific mRNA and Protein Expression in Humans

Population Pharmacokinetics Modeling of Unbound Efavirenz, Atazanavir, and Ritonavir in HIV‐Infected Subjects With Aging Biomarkers

Systemic low-grade inflammation is related to both circulating and adipose tissue TNFα, leptin and IL-6 levels in obese women

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