Orosomucoid serum concentrations and fat depot-specific mRNA and protein expression in humans

Abstract

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 site-specific 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.

Fig. 1.

Correlation of serum ORM concentration and (A) BMI (n = 64), (B) % body fat (n = 61), and (C) serum leptin concentration (n = 56). Serum ORM and leptin concentrations were log transformed to achieve normal distribution.

Fig. 2.

ORM mRNA expression and protein expression in human VAT and SAT. (A) Total RNA of paired samples from VAT and SAT was quantified using real-time PCR. Mean ORM mRNA expression was not significantly different between VAT and SAT (n = 20). (B) ORM protein expression of paired samples from VAT and SAT was analyzed by Western blot. Mean ORM protein expression was not significantly different between VAT and SAT (n = 18).

Fig. 3.

Correlation of VAT ORM mRNA expression and (A) VAT adiponectin mRNA expression (n = 18), (B) VAT TNF-α mRNA expression (n = 17), and (C) VAT IL-6 mRNA expression (n = 16). Correlation of SAT ORM mRNA expression and (D) SAT adiponectin mRNA expression (n = 20), (E) SAT TNF-α mRNA expression (n = 20), and (F) SAT IL-6 mRNA expression (n = 20)