Parallel downregulation of retinol-binding protein-4 and adiponectin expression in subcutaneous adipose tissue of non-morbidly obese subjects

Abstract

Context and objective: Adipokines are involved in the etiopathology of obesity-related disorders. Since the role of adipokine retinol-binding protein-4 (RBP4) in obesity remains uncertain and its relationship with other adipokines and inflammatory markers has not been examined in detail, we investigated the relationships of RBP4 mRNA expression and circulating protein levels with obesity, anthropometric and metabolic variables, as well as with obesity-related inflammatory markers adiponectin and C-reactive protein. Subjects and methods:One-hundred and twenty-five subjects participated, 36 lean (body mass index (BMI): !25 kg/m 2 ) and 89 obese (overweight/obese; BMI: R25!40) whose anthropometric and metabolic variables were assessed. mRNA expression was quantified by real-time PCR in subcutaneous adipose tissue (s.c.-AT) of 46 subjects. Results: There was a tendency for circulating RBP4 levels to positively correlate with waist circumference (bZ0.29, PZ0.08; R 2 Z0.08), but there was no significant association with the obesity-related parameters analysed. RBP4 and adiponectin mRNA expression levels were similarly downregulated in the s.c.-AT of obese subjects (0.5-fold); however, RBP4 downregulation did not affect its circulating protein levels. The expression of RBP4 and adiponectin was positively correlated even after controlling for confounding factors (bZ0.59, P!0.0001; R 2 Z0.40). Conclusions: In our population, RBP4 circulating levels were not significantly correlated with obesityrelated parameters, although a tendency to correlate with waist circumference suggests a relationship with insulin resistance and other metabolic disorders. In addition, our results suggest that the production of RBP4 by other tissues such as liver, rather than s.c.-AT, may be involved in regulating RBP4 circulating levels.

Association of Retinol-Binding Protein-4 (RBP4) with Lipid Parameters in Obese Women

“…This is in agreement with our previous finding in nonmorbidly obese patients, where RBP4 was found to be unrelated to CRP or adiponectin [39]. The lack of an association between RBP4 and circulating levels of inflammatory parameters does not allow any relationship to be established between this adipokine and the low-grade of inflammation measured in the population studied.…”

“…Although both express RBP4, we found no association between RBP4 and adiposity measurements. This is in agreement with the absence of a correlation between RBP4 systemic levels and its expression in subcutaneous adipose tissue in lean and obese subjects found by us and by other authors [17,39]. It has also been suggested that hepatocytes contribute to a large proportion of systemic RBP4 protein concentration in humans as what happens in rodents, where the liver is the key organ involved in regulating circulating RBP4 levels [40][41][42].…”

Human RBP4 adipose tissue expression is gender specific and influenced by leptin

“…In rodents, plasma and liver RBP4 concentrations were lowered by lipopolysaccharide‐induced acute inflammation 31 . However, consistent with our observation, a more recent study in humans failed to find an association of systemic levels of RBP4 with markers of obesity induced inflammation 32 …”

Retinol binding protein 4 – a novel association with early-onset preeclampsia

“…The lack of correlation between circulating RBP4 concentrations and obesity-related parameters demonstrated in our study and those of others[117, 124], leads to the suggestion that the liver, rather than adipose tissue, may be involved in regulating the circulating RBP4 concentration[13]. It may be that the differences in the RBP4 concentration between normal pregnant women and those with early-onset preeclampsia are related to liver dysfunction.…”