Retinol-Binding Protein 4 Induces Hepatic Mitochondrial Dysfunction and Promotes Hepatic Steatosis

Liu, Yan; Mu, Di; Chen, Hongen; Li, Di; Song, Jiayi; Yuan, Zuyi; Xia, Min

doi:10.1210/jc.2016-1320

Cited by 33 publications

(37 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adeno‐associated viral overexpression of RBP4 in liver does not impair whole body glucose tolerance in mice but serum RBP4 levels were not elevated in that study and hepatic insulin sensitivity was not assessed . Finally, adipocyte‐selective overexpression of RBP4 and global overexpression of RBP4 both result in glucose intolerance and increased hepatic lipid accumulation even on a chow diet …”

Section: Discussionmentioning

confidence: 75%

“…In humans, one study showed no difference in hepatic RBP4 mRNA expression between 45 obese women and 4 lean controls . However, a recent study indicated that both mRNA and protein levels of RBP4 are increased in liver of humans with nonalcoholic fatty liver disease and RBP4 mRNA expression correlates with hepatic triglyceride content . Adeno‐associated viral overexpression of RBP4 in liver does not impair whole body glucose tolerance in mice but serum RBP4 levels were not elevated in that study and hepatic insulin sensitivity was not assessed .…”

Section: Discussionmentioning

confidence: 77%

See 1 more Smart Citation

RBP4 increases lipolysis in human adipocytes and is associated with increased lipolysis and hepatic insulin resistance in obese women

et al. 2020

View full text Add to dashboard Cite

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. AbstractRetinol-binding protein-4 (RBP4) is elevated in serum and adipose tissue (AT) in obesity-induced insulin resistance and correlates inversely with insulin-stimulated glucose disposal. But its role in insulin-mediated suppression of lipolysis, free fatty acids (FFA), and endogenous glucose production (EGP) in humans is unknown. RBP4 mRNA or protein levels were higher in liver, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in morbidly obese subjects undergoing Roux-en-Y gastric bypass surgery compared to lean controls undergoing elective laparoscopic cholecystectomy. RBP4 mRNA expression in SAT correlated with the expression of several macrophage and other inflammation markers. Serum RBP4 levels correlated inversely with glucose disposal and insulin-mediated suppression of lipolysis, FFA, and EGP. Mechanistically, RBP4 treatment of human adipocytes in vitro directly stimulated basal lipolysis. Treatment of adipocytes with conditioned media from RBP4-activated macrophages markedly increased basal lipolysis and impaired insulin-mediated lipolysis suppression. RBP4 treatment of macrophages increasedTNFα production. These data suggest that elevated serum or adipose tissue RBP4 levels in morbidly obese subjects may cause hepatic and systemic insulin resistance by stimulating basal lipolysis and by activating macrophages in adipose tissue, resulting in release of pro-inflammatory cytokines that impair lipolysis suppression. While we have demonstrated this mechanism in human adipocytes in vitro, and correlations from our flux studies in humans strongly support this, further studies are needed 6100 |

show abstract

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 77%

RBP4 increases lipolysis in human adipocytes and is associated with increased lipolysis and hepatic insulin resistance in obese women

et al. 2020

View full text Add to dashboard Cite

show abstract

“…This suggests that RBP4 might play an important role in the disturbance of lipid synthesis in the liver, related to insulin resistance, and perhaps is a surrogate marker of liver steatosis. It was shown that RBP4 expression was aberrantly elevated in non-alcoholic fatty liver disease (NAFLD) in middle-age human and animal models, as well as positively associated with hepatic mitochondrial dysfunction combined with increased hepatic triglyceride accumulation [ 45 , 46 ]. In vitro studies showed that RBP4 stimulated lipogenesis in HepG2 cells in a dose-dependent manner [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Components of metabolic syndrome in relation to plasma levels of retinol binding protein 4 (RBP4) in a cohort of people aged 65 years and older

Majerczyk

Kocełak

Choręża

et al. 2018

J Endocrinol Invest

View full text Add to dashboard Cite

PurposeElevated plasma concentration of retinol binding protein 4 (RBP4) has recently emerged as a potential risk factor as a component of developing metabolic syndrome (MS). Therefore, this study aimed to analyse the relationship between components of MS and concentrations of plasma RBP4 in a population of subjects 65 years and older.MethodsThe study sample consisted of 3038 (1591 male) participants of the PolSenior study, aged 65 years and older. Serum lipid profile, concentrations of RBP4, glucose, insulin, C-reactive protein, IL-6, and activity of aminotransferases were measured. Nutritional status (BMI/waist circumference) and treatment with statins and fibrates were evaluated. Glomerular filtration rate (eGFR), de Ritis ratio, and fatty liver index (FLI), as well as HOMA-IR were calculated.ResultsOur study revealed a strong relationship between components of MS and RBP4 in both sexes: plasma RBP4 levels were increased in men by at least 3×, and in women by at least 4×. Hypertriglyceridemia was most strongly associated with elevated plasma RBP4 levels. Multivariate, sex-adjusted regression analysis demonstrated that chronic kidney disease [OR 1.86 (95% CI 1.78–1.94)], hypertriglyceridemia [OR 1.52 (1.24–1.87)], hypertension [OR 1.15 (1.12–1.19)], low serum HDL cholesterol [OR 0.94 (0.92–0.97)], and age > 80 years [OR 0.86 (0.81–0.90)] were each independently associated with RBP4 concentration (all p < 0.001).ConclusionsIn Caucasians 65 years and older, RBP4 serum levels are associated with a number of components of MS, independent of sex and kidney function. Hypertriglyceridemia as a component of MS is most significantly related to RBP4 concentration.

show abstract

“…2,26,27 Serum RBP can promote hepatic steatosis by inducing hepatic mitochondrial dysfunction. 28 Besides, Yang et al suggested that there might be retinol-independent mechanisms for RBP through influencing insulin resistance. 27 The other possible mechanism linking the increased urine RBP levels with NAFLD is the inflammatory response T A B L E 1 Anthropometric and biochemical features of the study subjects during the "second hit" phase of NAFLD pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Association between urine retinol‐binding protein levels and nonalcoholic fatty liver disease: A cross‐sectional study in Chinese population

Zhang

Liu

Zhang

et al. 2017

Clinical Laboratory Analysis

View full text Add to dashboard Cite

show abstract

Retinol-Binding Protein 4 Induces Hepatic Mitochondrial Dysfunction and Promotes Hepatic Steatosis

Abstract: These results have unraveled a novel role of RBP4 in hepatic mitochondrial dysfunction and steatosis and suggest that RBP4 might be a potential target for the early prevention of NAFLD.

Cited by 33 publications

References 37 publications

RBP4 increases lipolysis in human adipocytes and is associated with increased lipolysis and hepatic insulin resistance in obese women

RBP4 increases lipolysis in human adipocytes and is associated with increased lipolysis and hepatic insulin resistance in obese women

Components of metabolic syndrome in relation to plasma levels of retinol binding protein 4 (RBP4) in a cohort of people aged 65 years and older

Association between urine retinol‐binding protein levels and nonalcoholic fatty liver disease: A cross‐sectional study in Chinese population

Contact Info

Product

Resources

About