Circulating and liver tissue levels of retinol‐binding protein‐4 in non‐alcoholic fatty liver disease

Schina, Maria; Koskinas, John; Tiniakos, Dina; Hadziyannis, Emilia; Savvas, Savvas; Karamanos, B.; Manesis, Emanuel K.; Archimandritis, Athanasios

doi:10.1111/j.1872-034x.2009.00534.x

Cited by 39 publications

(51 citation statements)

References 33 publications

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“…This discrepancy may be due to the analysis of RBP4 expression in different adipose tissues: visceral adipose tissue in this study while subcutaneous adipose tissue in the human patients' study. Surprisingly, we did not find a change of RBP4 expression in the liver in response to either high fat diet or pioglitazone treatment, although RBP4 is abundantly expressed in the liver and secreted into the circulation in a 1:1:1 complex with retinol (holo-RBP4) and transthyretin [26]. This finding from the in vivo tissues was confirmed by the in vitro cell culture experiment wherein pioglitazone inhibited RBP4 expression only in adipocytes, but not hepatocytes.…”

Section: Discussionsupporting

confidence: 68%

Pioglitazone Lowers Serum Retinol Binding Protein 4 by Suppressing its Expression in Adipose Tissue of Obese Rats

Zhu

Xiao²,

Liu³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Pioglitazone, a peroxisome proliferator-activated receptor γ activator, is clinically used to treat insulin resistance. However, the underlying mechanism of pioglitazone's action remains unclear. We investigated whether, and how, pioglitazone modulates serum level of retinol binding protein 4 (RBP4), an adipocytokine associated with obesity and insulin resistance. Methods: Insulin sensitivity was determined by oral glucose tolerance test, and RBP4 expression was detected by RT-PCR and Western blotting. Results: Pioglitazone treatment significantly decreased serum RBP4 levels in obese rats, which was correlated with reduced body weight and increased insulin sensitivity. Moreover, pioglitazone greatly decreased RBP4 mRNA and protein levels in adipose tissue but not in the liver. Consistently, pioglitazone treatment significantly reduced RBP4 protein expression in 3T3-L1 adipocytes but not in HepG2 cells. Conclusion: These results demonstrate that pioglitazone inhibits the level of serum RPB4 by suppressing RBP4 expression in adipose tissue of obese rats, suggesting that inhibiting RBP4 expression in adipocytes may provide a mechanism by which pioglitazone improves insulin sensitivity in insulin-resistant subjects.

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Section: Discussionsupporting

confidence: 68%

Pioglitazone Lowers Serum Retinol Binding Protein 4 by Suppressing its Expression in Adipose Tissue of Obese Rats

Zhu

Xiao²,

Liu³

et al. 2015

Cell Physiol Biochem

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“…It is notable that our findings were in accordance with observations from previous studies [14][15][16][17][18][19][20], which demonstrated that serum RBP4 levels were lower in patients with chronic liver diseases and the levels decreased as the diseases progressed to more severe stages. Nevertheless, recent investigations have shown that serum RBP4 levels are higher in patients with non-alcoholic fatty liver disease and chronic hepatitis C and these levels increase with the degree of liver steatosis [12,13].…”

Section: Discussionsupporting

confidence: 95%

“…Both animal and human studies have shown that RBP4 might be involved in the development of insulin resistance and diabetes [10,11]. Serum levels of RBP4 have been previously shown to be associated with the degree of steatosis and fibrosis in liver diseases of various etiologies, such as non-alcoholic fatty liver disease and chronic hepatitis C [12][13][14][15][16][17][18][19][20]. However, the precise mechanism of RBP4 influence on liver fibrogenesis is not clearly understood.…”

Section: Introductionmentioning

confidence: 97%

Serum retinol binding protein 4 and clinical outcome in postoperative biliary atresia

et al. 2011

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“…Circulating rbp4 has been shown to correlate positively with nonalcoholic fat liver disease in some studies, 17,18 but not others. 27,28 However, most of those studies have been performed in limited numbers of subjects. Our study, performed in a large population of patients with T2DM using a precise evaluation of liver fat content by proton magnetic resonance spectroscopy, does not find any significant association between plasma rbp4 and liver fat content.…”

Section: Discussionmentioning

confidence: 99%

Retinol-Binding Protein 4 Is an Independent Factor Associated With Triglycerides and a Determinant of Very Low-Density Lipoprotein–Apolipoprotein B100 Catabolism in Type 2 Diabetes Mellitus

Vergès

Guiu

Cercueil

et al. 2012

ATVB

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Objective-Retinol-binding protein 4 (rbp4) is an adipokine secreted by adipocytes and liver, whose levels are elevated in type 2 diabetes mellitus (T2DM). Plasma levels of rbp4 and triglycerides are strongly correlated in T2DM. However, we do not know whether this association is direct or indirect via liver fat content, and the link between rbp4 and triglyceride metabolism remains unknown. Methods and Results-Liver fat measurement by proton spectroscopy was performed in 221 patients with T2DM, and an in vivo kinetic study with stable isotopes was carried out in 14 patients with T2DM. In multivariate analysis, triglycerides were associated positively with rbp4 (β=0.273, P<0.0001), apolipoprotein (apo) B (β=0.258, P<0.0001), and liver fat (β=0.191, P=0.002) and negatively with high-density lipoprotein cholesterol (β=−0.442, P<0.0001). rbp4 was correlated positively with apoB100 very-low-density lipoprotein (VLDL) pool (r=0.62, P=0.017) and negatively with VLDLapoB100 total fractional catabolic rate (r=−0.66, P=0.001). In multivariate analysis, rbp4 (P=0.015), plasma triglycerides (P=0.024), and sex (P=0.026) were independently associated with VLDL-apoB100 total fractional catabolic rate. Conclusion-In T2DM, plasma rbp4 level is associated with plasma triglycerides, independently of liver fat content. There is a strong independent negative correlation between plasma rbp4 and VLDL-apoB100 total fractional catabolic rate. These data suggest that rbp4 may be involved in the pathophysiology of hypertriglyceridemia in T2DM by reducing VLDL catabolism. (Arterioscler Thromb Vasc Biol. 2012;32:3050-3057.)

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Circulating and liver tissue levels of retinol‐binding protein‐4 in non‐alcoholic fatty liver disease

Abstract: In NAFLD patients, serum RBP4 was significantly lower as compared with controls and did not correlate with insulin resistance. In contrast, RBP4 liver tissue expression was enhanced and correlated with NAFLD histology.

Cited by 39 publications

References 33 publications

Pioglitazone Lowers Serum Retinol Binding Protein 4 by Suppressing its Expression in Adipose Tissue of Obese Rats

Pioglitazone Lowers Serum Retinol Binding Protein 4 by Suppressing its Expression in Adipose Tissue of Obese Rats

Serum retinol binding protein 4 and clinical outcome in postoperative biliary atresia

Retinol-Binding Protein 4 Is an Independent Factor Associated With Triglycerides and a Determinant of Very Low-Density Lipoprotein–Apolipoprotein B100 Catabolism in Type 2 Diabetes Mellitus

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