Elevated Retinol Binding Protein 4 Induces Apolipoprotein B Production and Associates With Hypertriglyceridemia

Yan, Liying; Chen, Hongen; Wang, Jingjing; Sun, Ruifang; Xia, Min

doi:10.1210/jc.2015-1072

Cited by 5 publications

(2 citation statements)

References 40 publications

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“…Although these findings suggest that there may be subgroups in the population with CVD where elevated retinol concentrations can be particularly harmful, the interaction of retinol with common risk factors of CVD and other diseases should be evaluated in other, preferably healthy cohorts. It would also be useful to assess whether these interactions are present also for RBP4 and retinoic acid in humans, especially considering that data exist that link RBP4 to lipoprotein metabolism (11,33,99,104) and retinoic acid to homocysteine metabolism (105)(106)(107)(108)(109)(110).…”

Section: Serum Retinol -New Hypotheses and Old Challengesmentioning

confidence: 99%

Retinol, Retinoic Acid, and Retinol-Binding Protein 4 are Differentially Associated with Cardiovascular Disease, Type 2 Diabetes, and Obesity: An Overview of Human Studies

Olsen

Blomhoff

2020

Advances in Nutrition

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Vitamin A is a fat-soluble essential nutrient obtained from plant- and animal-based sources that has roles in growth, vision, and metabolism. Vitamin A circulates mainly as retinol bound to retinol-binding protein 4 (RBP4), and is delivered to tissues and converted to retinoic acid, which is a ligand for several nuclear receptors. In recent years, aspects of vitamin A metabolism have been under scrutiny with regards to the development of metabolic and lifestyle diseases including cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and overweight and obesity in humans. Studies have mainly focused on RBP4 in this context, whereas the major circulating form, retinol, and the major bioactive form, retinoic acid, have been overlooked in this regard until recently. As one of the main roles of RBP4 is to deliver retinol to tissues for biological action, the associations of retinol and retinoic acid with these diseases must also be considered. In this review, we summarize and discuss recent and available evidence from human studies with focus on retinol, retinoic acid, and RBP4 and provide an overview of these crucial components of vitamin A metabolism in CVD, T2DM, and obesity. In summary, retinol was found to be both inversely and positively associated with CVD whereas the associations with T2DM and obesity were less clear. Although only a few studies have been published on retinoic acid, it was inversely associated with CVD. In contrast, serum RBP4 was mostly found to be positively associated with CVD, T2DM, and obesity. At present, it is difficult to ascertain why the reported associations differ depending on the compound under study, but there is a clear imbalance in the literature in disfavor of retinol and retinoic acid, which needs to be considered in future human studies.

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Section: Serum Retinol -New Hypotheses and Old Challengesmentioning

confidence: 99%

Retinol, Retinoic Acid, and Retinol-Binding Protein 4 are Differentially Associated with Cardiovascular Disease, Type 2 Diabetes, and Obesity: An Overview of Human Studies

Olsen

Blomhoff

2020

Advances in Nutrition

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“…Apart from the positive relationship between serum RBP4 and Th17/Treg imbalance, the current study also found that increased serum RBP4 was associated with hyperlipidemia, CVD, and recurrent stroke in stroke patients. Possible explanations are: (1) RBP4 increased the level of blood lipids by inducing apolipoprotein B production ( 28 ). Therefore, elevated serum RBP4 was associated with the occurrence of hyperlipidemia in stroke patients.…”

Section: Discussionmentioning

confidence: 99%

Serum retinol-binding protein 4 in stroke patients: correlation with T helper 17/regulatory T cell imbalance and 3-year cognitive function decline

Wang,

Qin,

2023

Front. Neurol.

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ObjectiveRetinol-binding protein 4 (RBP4) promotes atherosclerotic progression and neuronal loss, whereas its association with cognitive impairment in stroke is unclear. Hence, this prospective study aimed to explore the association of serum RBP4 with the T helper (Th)17/regulatory T (Treg) cell ratio and its correlation with cognitive impairment in stroke patients.MethodsPeripheral blood samples from 265 stroke patients and 50 healthy controls (HCs) were collected at enrollment for serum RBP4 (by enzyme-linked immunosorbent assay) and Th17 and Treg cells (by flow cytometry) determination. Additionally, stroke patients underwent routine follow-ups, and their Mini-Mental State Examination (MMSE) scores were assessed at baseline and in years 1, 2, and 3 after enrollment.ResultsSerum RBP4 was elevated in stroke patients compared to HCs (p < 0.001), with a good ability to differentiate stroke patients from HCs (area under the curve: 0.815). Serum RBP4 was positively associated with Th17 cells (p < 0.001) and the Th17/Treg cell ratio (p < 0.001) and negatively associated with Treg cells (p = 0.003) in stroke patients, whereas it was only positively associated with the Th17/Treg cell ratio (p = 0.027) but not with Th17 (p = 0.075) or Treg (p = 0.130) cells in HCs. Furthermore, increased serum RBP4 was associated with a lower MMSE score (p < 0.001) and a lower incidence of cognition impairment (p = 0.005) at enrollment in stroke patients, as were Th17 cells and the Th17/Treg cell ratio (all p < 0.050). The 1-, 2-, and 3-year MMSE scores in stroke patients were 25.9 ± 2.0, 25.3 ± 2.3, and 24.9 ± 2.3, respectively. More importantly, serum RBP4 was negatively correlated with 1-, 2-, and 3-year MMSE scores (all p < 0.001) and positively associated with 1-year (p = 0.013), 2-year (p = 0.007), and 3-year (p = 0.001) MMSE score declines in stroke patients.ConclusionSerum RBP4 is positively associated with a Th17/Treg cell imbalance and, more importantly, it is indicative of cognitive function decline within 3 years in stroke patients. Thus, early and timely interventions and physical rehabilitation are more necessary in stroke patients with high serum RBP4.

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The relationship between retinol-binding protein 4 and apolipoprotein B-containing lipoproteins is attenuated in patients with very high serum triglycerides: A pilot study

et al. 2016

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Elevated Retinol Binding Protein 4 Induces Apolipoprotein B Production and Associates With Hypertriglyceridemia

Abstract: Elevated circulating RBP4 concentrations were associated with higher risk of hypertriglyceridemia by inducing the secretion of triglyceride-rich apoB-containing lipoproteins.

Cited by 5 publications

References 40 publications

Retinol, Retinoic Acid, and Retinol-Binding Protein 4 are Differentially Associated with Cardiovascular Disease, Type 2 Diabetes, and Obesity: An Overview of Human Studies

Retinol, Retinoic Acid, and Retinol-Binding Protein 4 are Differentially Associated with Cardiovascular Disease, Type 2 Diabetes, and Obesity: An Overview of Human Studies

Serum retinol-binding protein 4 in stroke patients: correlation with T helper 17/regulatory T cell imbalance and 3-year cognitive function decline

The relationship between retinol-binding protein 4 and apolipoprotein B-containing lipoproteins is attenuated in patients with very high serum triglycerides: A pilot study

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