All-trans Retinoic Acid Lowers Serum Retinol-Binding Protein 4 Concentrations and Increases Insulin Sensitivity in Diabetic Mice

Manolescu, Daniel-Constantin; Sima, Aurélia; Bhat, Pangala V.

doi:10.3945/jn.109.115147

Cited by 71 publications

(53 citation statements)

References 45 publications

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“…[15][16][17][18][19][20][21][22][23][24] On the opposite, in the present study a three-fold excess of vitamin A intake in early life (day 1 to day 20 of life) exacerbated WAT expansion in response to a HF diet later in life. The reason(s) of this apparent discrepancy is unknown but could relate to concentration-dependent effects, because studies in adult animals typically used relatively high retinoid concentrations (reviewed in 10 ).…”

Section: Discussionmentioning

confidence: 41%

“…9,10 Retinoic acid (RA), its acid form, potently blocks adipogenesis of cultured preadipose cells when introduced at early stages of the differentiation process, 11 although other reports indicate that RA at low doses may in fact promote adipogenesis. [12][13][14] Studies in adult rodents treated with RA [15][16][17][18][19][20][21][22][23] or retinaldehyde 24 sustain an antiadiposity action of vitamin A derivatives in vivo. Furthermore, results from animal studies 16,[25][26][27][28] and human observational studies 29,30 point to an inverse relationship between vitamin A status and body fat content.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin A supplementation in early life affects later response to an obesogenic diet in rats

et al. 2012

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OBJECTIVE:To assess the influence of supplementation with a moderate dose of vitamin A in early life on adipose tissue development and the response to an obesogenic diet later in life. METHODS: During the suckling period, rat pups received a daily oral dose of retinyl palmitate corresponding to three times the vitamin A ingested daily from maternal milk. Control rats received the vehicle (olive oil). Short-term effects of treatment on gene expression and morphology of white adipose tissue (WAT) were analyzed in animals on the day after weaning (day 21). To study long-term effects, control and vitamin A-treated rats were fed, after weaning, a normal fat or a high-fat (HF) diet for 16 weeks. RESULTS: WAT of vitamin A-treated young rats (day 21) was enriched in small adipocytes with a reduced expression of adipogenic markers (peroxisome proliferator-activated receptor g and lipoprotein lipase) and an increased cell proliferation potential as indicated by increased expression of proliferating cell nuclear antigen. Increased retinoic acid (RA)-induced transcriptional responses were present in the tissues of vitamin A-treated young rats (day 21) including WAT. Vitamin A-treated rats developed higher adiposity than control rats on a HF diet as indicated by body composition analysis and increased WAT depot mass, adipocyte diameter, WAT DNA content, leptinemia and adipose leptin gene expression. Excess adiposity gain in vitamin A-treated rats developed in the absence of changes in body weight and was attributable to excess adipocyte hyperplasia. No differences in adiposity were observed between vitamin A-treated rats and control rats on a normal fat diet. Total retinol levels in WAT of vitamin A-treated rats were elevated at weaning (day 21) and normalized by day 135 of age. CONCLUSION: Vitamin A intake in the early stages of postnatal life favors subsequent HF diet-induced adiposity gain through mechanisms that may relate to changes in adipose tissue development, likely mediated by RA.

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Section: Discussionmentioning

confidence: 41%

Section: Introductionmentioning

confidence: 99%

Vitamin A supplementation in early life affects later response to an obesogenic diet in rats

et al. 2012

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“…Corroborating with the above observations, supplementation of retinoic acid to ob/ob mice reduced plasma RBP4 levels by increasing its renal clearance and thus improving insulin sensitivity (10). Furthermore, genetic polymorphisms in RBP4 are also found to be associated with higher risk of development of T2D (11).…”

Section: Rbp4 and Its Link To Diabetesmentioning

confidence: 54%

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

et al. 2012

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SummaryRetinol-binding protein 4 (RBP4) is the principle carrier of retinol in the human plasma, which circulates as a complex with transthyretin (TTR), a homotetrameric thyroxine transport protein. Although this complex formation is thought to prevent glomerular filtration of RBP4, it also stabilizes the quaternary structure of TTR. Recent studies indicate elevated plasma levels of RBP4 in type 2 diabetes (T2D). In contrast, reduced RBP4 levels were observed in type 1 diabetes (T1D). Herein, we critically examine the probable mechanisms involved in the regulation of RBP4 and TTR levels during T2D and T1D. The available evidences point to the involvement of pancreatic factors in regulating the expression of both RBP4 and TTR. It appears that during T1D, TTR levels are reduced and it exists predominantly as a monomer that may interfere its interaction with RBP4 resulting in its loss through glomerular filtration. However, plasma TTR levels remain high under T2D conditions and thus reducing glomerular filtration of RBP4. Therefore, the plasma TTR levels appear to be an important determinant of plasma RBP4 levels in these two diabetic conditions. 2012 IUBMB IUBMB Life, 64(12): 975-982, 2012

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“…ERK1/2, p38, and STAT-JAK) or the receptor is being down-regulated leading to impairment of all subsequent pathways. Furthermore, studies have indicated that retinoic acid can induce peroxisome proliferator-activated receptor g (PPARg) and thus lead to an insulin-sensitized cell (Krskova-Tybitanclova et al 2008, Macejova et al 2009, Manolescu et al 2010. We hypothesized that retinoic acid is capable of down-regulating the AT1 itself; if the AT1 is being down-regulated, it may be due to increased insulin sensitivity and increased intracellular glucose uptake.…”

Section: Introductionmentioning

confidence: 99%

13-cis-Retinoic acid specific down-regulation of angiotensin type 1 receptor in rat liver epithelial and aortic smooth muscle cells

Snyder

Thekkumkara²

2011

Journal of Molecular Endocrinology

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Transcriptional repression through cis-and trans-acting factors enabling an alternate approach to control angiotensin type 1 receptor (AT1 or AGTR1 as listed in the MGI database) expression has not been studied. In previous investigations, treatment with retinoic acid was found to be associated with enhanced insulin sensitivity. In our previous study, expression of AT1 was found to be inversely correlated with intracellular glucose concentrations. Therefore, we hypothesized that 13-cis-retinoic acid (13cRA), an antioxidant, enhances insulin-sensitive glucose-mediated downregulation of the AT1. In this study, we used continuously passaged rat liver epithelial cells. Our study shows that cells exposed to 13cRA specifically down-regulated the AT1 protein in a dose-and time-dependent manner, independently of any change in receptor affinity. Down-regulation of the AT1 expression leads to reduced AngII-mediated intracellular calcium release, a hallmark of receptor-mediated intracellular signaling. Similarly with receptor down-regulation, we observed a significant reduction in AT1 mRNA; however, the AT1 down-regulation was independent of insulin-sensitive glucose uptake and retinoic acid receptor activation (RAR/RXR). Treatment with 13cRA resulted in phosphorylation of p42/p44 MAP kinases in these cells. Subsequent studies using MEK inhibitor PD98059 prevented 13cRA-mediated AT1 down-regulation and restored AngII-mediated intracellular calcium response. Furthermore, 13cRA-mediated inhibitory effects on AT1 were validated in primary rat aortic smooth muscle cells. In summary, our results demonstrate for the first time that 13cRA has a glucose-and RAR/RXR-independent mechanism for transcriptional inhibition of AT1, suggesting its therapeutic potential in systems in which AT1 expression is deregulated in insulin-sensitive and -insensitive tissues.

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All-trans Retinoic Acid Lowers Serum Retinol-Binding Protein 4 Concentrations and Increases Insulin Sensitivity in Diabetic Mice

Cited by 71 publications

References 45 publications

Vitamin A supplementation in early life affects later response to an obesogenic diet in rats

Vitamin A supplementation in early life affects later response to an obesogenic diet in rats

Contrasting effects of type 2 and type 1 diabetes on plasma RBP4 levels: The significance of transthyretin

13-cis-Retinoic acid specific down-regulation of angiotensin type 1 receptor in rat liver epithelial and aortic smooth muscle cells

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