Retinol binding protein 4 and its membrane receptors: a metabolic perspective

Fedders, Ronja; Muenzner, Matthias; Schupp, Michael

doi:10.1515/hmbci-2015-0013

Cited by 18 publications

(20 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RBP4 and its associated RA have been shown to trigger several downstream pathways to confer insulin resistance [ 16 – 19 ]. The pathways could also be shared in promoting cancer metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Cumulative evidences showed that overexpression of RBP4 from adipose tissues promote hyperinsulinemia and type II diabetes [ 11 – 15 ]. Several pathways have been identified mediate RBP4 signaling [ 16 ]. RA and its oxidative products can activate retinoic acid receptors and retinoid X receptors and promote glucose production in liver [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adipokine RBP4 drives ovarian cancer cell migration

Wang

Zhang

2018

J Ovarian Res

View full text Add to dashboard Cite

BackgroundObesity has been linked to several types of cancers including ovarian cancer. Retinol binding protein 4 (RBP4) is an adipokine that drives the development of hyperinsulinemia and type II diabetes in obesity patients and animals. Previously, we have identified RBP4 as a serum marker for ovarian cancer. Here we further explored the consequence of RBP4 upregulation in ovarian cancer cells and its molecular mechanism.ResultsOur results show that RBP4 is overexpressed in ovarian cancer cells to the same extent as in adipose tissues. The overexpression of RBP4 in ovarian cancer cells promotes cancer cell migration and proliferation. At molecular level, cancer progression factors MMP2 and MMP9 are induced in response to RBP4 overexpression. We further investigated which signaling pathways are utilized by RBP4 to activate ovarian cancer cell migration. We found RhoA/Rock1 pathway is turned on and CyclinD1 is upregulated in RBP4 overexpressed cells. Inhibition of RhoA/Rock1 pathway reduces the RBP4-induced MMP2 and MMP9 expression. The RBP4 action is depend on its associated ligand vitamin A/retinol acid (RA) and possibly involves similar pathways as for conferring insulin resistance. Moreover, we show that knockdown of RBP4 significantly reduce cancer cell migration and proliferation as well as expressions of oncogenic factors.ConclusionsOur results indicated that RBP4 can drive ovarian cancer cell migration and proliferation via RhoA/Rock1 and ERK pathway. It suggests that RBP4 act as a oncogene in ovarian cancer cells. Thus, RBP4 could be a molecular bridge between obesity and cancers and a potential target for treating obese cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adipokine RBP4 drives ovarian cancer cell migration

Wang

Zhang

2018

J Ovarian Res

View full text Add to dashboard Cite

show abstract

“…In summary, we characterized a novel RBP4 gain-of-function mouse model and show that an elevation of liver-secreted RBP4 to serum levels as observed in the obese, insulin-resistant state does not impair glucose homeostasis in mice. Thus, although increased levels of circulating RBP4 associate with glucose intolerance and insulin resistance (12), they are unlikely to be a causative factor. However, RBP4 may exhibit local functions in organs such as adipose tissue whose investigation could help to reconcile the divergence of previous reports.…”

Section: Liver Rbp4 and Glucose Homeostasismentioning

confidence: 99%

“…These findings supported the notion of RBP4 working as adipokine, and it was hypothesized that an increased expression in adipose tissue of obese subjects leads to higher serum levels that, in turn, induce insulin resistance. So far, a variety of mechanisms of how RBP4 causes glucose intolerance and insulin resistance were reported (12), most prominently a RBP4-driven inflammatory response in adipose tissue involving the activation of antigen presentation and T cells (6,13,14).…”

mentioning

confidence: 99%

Liver-secreted RBP4 does not impair glucose homeostasis in mice

Fedders

Muenzner

Weber

et al. 2018

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Retinol-binding protein 4 (RBP4) is the major transport protein for retinol in blood. Recent evidence from genetic mouse models shows that circulating RBP4 derives exclusively from hepatocytes. Because RBP4 is elevated in obesity and associates with the development of glucose intolerance and insulin resistance, we tested whether a liver-specific overexpression of RBP4 in mice impairs glucose homeostasis. We used adeno-associated viruses (AAV) that contain a highly liver-specific promoter to drive expression of murine RBP4 in livers of adult mice. The resulting increase in serum RBP4 levels in these mice was comparable with elevated levels that were reported in obesity. Surprisingly, we found that increasing circulating RBP4 had no effect on glucose homeostasis. Also during a high-fat diet challenge, elevated levels of RBP4 in the circulation failed to aggravate the worsening of systemic parameters of glucose and energy homeostasis. These findings show that liver-secreted RBP4 does not impair glucose homeostasis. We conclude that a modest increase of its circulating levels in mice, as observed in the obese, insulin-resistant state, is unlikely to be a causative factor for impaired glucose homeostasis.

show abstract

“…This is an intriguing observation because of the recent identification of retinol-binding protein (RBP4) as an adipokine, as well as RBP4’s association with breast cancer (60–62). RBP4 secreted from the liver is the sole transport protein for retinol in the blood, with circulating levels of retinol tightly correlating with circulating RBP4 levels (63, 64).…”

Section: Discussionmentioning

confidence: 99%

Long-term Diet and Biomarker Changes after a Short-term Intervention among Hispanic Breast Cancer Survivors: The¡Cocinar Para Su Salud!Randomized Controlled Trial

Greenlee

Gaffney²,

Aycinena

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

Background Among Hispanic breast cancer (BC) survivors, we examined the long-term effects of a short-term culturally-based dietary intervention on increasing fruits/vegetables (F/V), decreasing fat and changing biomarkers associated with BC recurrence risk. Methods Spanish-speaking women (n=70) with a history of stage 0-III BC who completed treatment were randomized to ¡Cocinar Para Su Salud! (n=34), a culturally-based 9-session program (24 hours over 12 weeks, including nutrition education, cooking classes, and food-shopping field trips), or a control group (n=36, written dietary recommendations for BC survivors). Diet recalls, fasting blood, and anthropometric measures were collected at baseline, 6, and 12 months. We report changes between groups at 12 months in dietary intake and biomarkers using 2-sample Wilcoxon t-tests and Generalized Estimating Equation (GEE) models. Results At 12 months, the intervention group compared to the control group reported higher increases in mean daily F/V servings (total: +2.0 vs. −0.4; P=0.006), and non-significant decreases in percent calories from fat (−2.2% vs. −1.1%; P=0.69) and weight (−2.6 kg vs. −1.5 kg; P=0.56). Compared to controls, participants in the intervention group had higher increases in plasma lutein (+20.4% vs. −11.5%; P=0.002), and borderline significant increases in global DNA methylation (+0.8% vs. −0.5%; P=0.06). Conclusions The short-term ¡Cocinar Para Su Salud! program was effective at increasing long-term F/V intake in Hispanic BC survivors and changed biomarkers associated with BC recurrence risk. Impact It is possible for short-term behavioral interventions to have long-term effects on behaviors and biomarkers in minority cancer patient populations. Results can inform future study designs.

show abstract

Retinol binding protein 4 and its membrane receptors: a metabolic perspective

Cited by 18 publications

References 104 publications

Adipokine RBP4 drives ovarian cancer cell migration

Adipokine RBP4 drives ovarian cancer cell migration

Liver-secreted RBP4 does not impair glucose homeostasis in mice

Long-term Diet and Biomarker Changes after a Short-term Intervention among Hispanic Breast Cancer Survivors: The¡Cocinar Para Su Salud!Randomized Controlled Trial

Contact Info

Product

Resources

About