Cellular retinol-binding protein type III is a PPARγ target gene and plays a role in lipid metabolism

Cellular retinol-binding protein (CRBP) type III (CRBP-III) belongs to the family of intracellular lipid-binding proteins, which includes the adipocyte-binding protein aP2. In the cytosol, CRBP-III binds retinol, the precursor of retinyl ester and the active metabolite retinoic acid. The goal of the present work is to understand the regulation of CRBP-III expression and its role in lipid metabolism. Using EMSAs, luciferase reporter assays, and chromatin immunoprecipitation assays, we found that CRBP-III is a direct target of peroxisome proliferator-activated receptor-γ (PPARγ). Moreover, CRBP-III expression was induced in adipose tissue of mice after treatment with the PPARγ agonist rosiglitazone. To examine a potential role of CRBP-III in regulating lipid metabolism in vivo, CRBP-III-deficient (C-III-KO) mice were maintained on a high-fat diet (HFD). Hepatic steatosis was decreased in HFD-fed C-III-KO compared with HFD-fed wild-type mice. These differences were partly explained by decreased serum free fatty acid levels and decreased free fatty acid efflux from adipose tissue of C-III-KO mice. In addition, the lack of CRBP-III was associated with reduced food intake, increased respiratory energy ratio, and altered body composition, with decreased adiposity and increased lean body mass. Furthermore, expression of genes involved in mitochondrial fatty acid oxidation in brown adipose tissue was increased in C-III-KO mice, and C-III-KO mice were more cold tolerant than wild-type mice fed an HFD. In summary, we demonstrate that CRBP-III is a PPARγ target gene and plays a role in lipid and whole body energy metabolism.

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Diet-related variation in cellular retinol-binding protein type II gene expression in rat jejunum

British Journal Of Nutrition ◽

10.1079/bjn20051575 ◽

2005 ◽

Vol 94 (6) ◽

pp. 890-895 ◽

Cited By ~ 5

Author(s):

Kazuhito Suruga ◽

Masaaki Kitagawa ◽

Hiromitsu Yasutake ◽

Sachiko Takase ◽

Toshinao Goda

Keyword(s):

Gene Expression ◽

Fatty Acid ◽

Binding Protein ◽

Dietary Fatty Acids ◽

Retinol Binding Protein ◽

Rat Jejunum ◽

Type Ii ◽

Feeding Period ◽

Related Variation ◽

Cellular Retinol Binding Protein

Cellular retinol-binding protein type II (CRBPII) is involved in the transport of vitamin A and its metabolism in the small intestine. In the present study, we demonstrated diet-related variations in CRBPII expression in rat jejunum. The CRBPII protein and mRNA levels increased in parallel after the start of feeding period regardless of whether the feeding period was restricted to the hours of darkness or of light. In addition, this variation was observed in the rats fed high-fat diet or low-fat diets, but not in those fed a fat-free diet or in fasted rats. A similar diet-induced variation was seen in the mRNA of liver-type fatty acid-binding protein in rat jejunum. In the transient transfection experiment, unsaturated fatty acid increased rat CRBPII gene promoter activity via the PPARα/retinoid X receptor-α heterodimer. Taken together, these results suggest that the diet-related variation in CRBPII expression in rat jejunum may be brought about by the transcriptional induction of CRBPII gene expression mainly triggered by dietary fatty acids.

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Enhanced Fatty Acid Flux Triggered by Adiponectin Overexpression

Endocrinology ◽

10.1210/en.2011-1339 ◽

2012 ◽

Vol 153 (1) ◽

pp. 113-122 ◽

Cited By ~ 23

Author(s):

Shoba Shetty ◽

Maria A. Ramos-Roman ◽

You-Ree Cho ◽

Jonathan Brown ◽

Jorge Plutzky ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Free Fatty Acid ◽

Uncoupling Protein ◽

Retinol Binding Protein ◽

Peroxisome Proliferator ◽

Tissue Mass ◽

Triglyceride Synthesis ◽

Peroxisome Proliferator Activated Receptor ◽

Brown Adipose

Adiponectin overexpression in mice increases insulin sensitivity independent of adiposity. Here, we combined stable isotope infusion and in vivo measurements of lipid flux with transcriptomic analysis to characterize fatty acid metabolism in transgenic mice that overexpress adiponectin via the aP2-promoter (ADNTg). Compared with controls, fasted ADNTg mice demonstrated a 31% reduction in plasma free fatty acid concentrations (P = 0.008), a doubling of ketones (P = 0.028), and a 68% increase in free fatty acid turnover in plasma (15.1 ± 1.5 vs. 25.3 ± 6.8 mg/kg · min, P = 0.011). ADNTg mice had 2-fold more brown adipose tissue mass, and triglyceride synthesis and turnover were 5-fold greater in this organ (P = 0.046). Epididymal white adipose tissue was slightly reduced, possibly due to the approximately 1.5-fold increase in the expression of genes involved in oxidation (peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor-γ coactivator 1α, and uncoupling protein 3). In ADNTg liver, lipogenic gene expression was reduced, but there was an unexpected increase in the expression of retinoid pathway genes (hepatic retinol binding protein 1 and retinoic acid receptor beta and adipose Cyp26A1) and liver retinyl ester content (64% higher, P < 0.02). Combined, these data support a physiological link between adiponectin signaling and increased efficiency of triglyceride synthesis and hydrolysis, a process that can be controlled by retinoids. Interactions between adiponectin and retinoids may underlie adiponectin's effects on intermediary metabolism.

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Free fatty acid binding protein-4 and retinol binding protein-4 in polycystic ovary syndrome: response to simvastatin and metformin therapies

Gynecological Endocrinology ◽

10.3109/09513590.2013.774360 ◽

2013 ◽

Vol 29 (5) ◽

pp. 483-487 ◽

Cited By ~ 5

Author(s):

Sidika E. Karakas ◽

Beata Banaszewska ◽

Robert Z. Spaczynski ◽

Leszek Pawelczyk ◽

Antoni Duleba

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Fatty Acid Binding Protein ◽

Polycystic Ovary ◽

Binding Protein ◽

Retinol Binding Protein ◽

Ovary Syndrome ◽

Fatty Acid Binding ◽

Retinol Binding Protein 4 ◽

Acid Binding Protein

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Structures of holo wild-type human cellular retinol-binding protein II (hCRBPII) bound to retinol and retinal

Acta Crystallographica Section D Biological Crystallography ◽

10.1107/s1399004714023839 ◽

2014 ◽

Vol 70 (12) ◽

pp. 3226-3232 ◽

Cited By ~ 10

Author(s):

Zahra Nossoni ◽

Zahra Assar ◽

Ipek Yapici ◽

Meisam Nosrati ◽

Wenjing Wang ◽

...

Keyword(s):

Intracellular Transport ◽

Binding Protein ◽

Binding Pocket ◽

Lipid Binding ◽

Retinol Binding Protein ◽

Binding Affinities ◽

Wild Type ◽

Intracellular Lipid ◽

X Ray ◽

Cellular Retinol Binding Protein

Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a noncanonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided.

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Zinc-α2-Glycoprotein Knockout Influenced Genes Expression Profile in Adipose Tissue and Decreased the Lipid Mobilizing After Dexamethasone Treatment in Mice

Hormone and Metabolic Research ◽

10.1055/a-1186-0649 ◽

2020 ◽

Vol 52 (10) ◽

pp. 755-763

Author(s):

Wenge Zhang ◽

Yu Qiao ◽

Fulei Qi ◽

Qingyi Shen ◽

Ruqian Zhao ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Fatty Acid ◽

Lipid Metabolism ◽

Gene Expression Profile ◽

Expression Profile ◽

Visceral Fat ◽

Fatty Acid Synthase ◽

Wild Type ◽

Genes Expression

AbstractZinc-α2-glycoprotein (ZAG), as an adipokine, plays an important role in lipid metabolism. However, its influence on whole gene expression profile in adipose tissue is not known. Under stress condition, how ZAG affects the lipid metabolism is also unclear. Therefore, in this study ZAG systemic knockout (KO) mice were used as a model to reveal the genes expression profile in visceral fat tissues of ZAG KO mice and wild-type mice by genome-wide microarray screening. Then dexamethasone (DEX) was used to explore the effect of ZAG deletion on body fat metabolism under stress. Our results showed that 179 genes were differentially expressed more than 1.5 times between ZAG KO mice and wild type mice, of which 26 genes were upregulated dramatically and 153 genes were significantly downregulated. Under DEX simulated stress, ZAG systemic knockout in vivo resulted in a markedly decrease of triglycerides (TG) and nonesterified fatty acid (NEFA) content in in plasma. Similarly, for lipid catabolism, ZAG KO led to a significant increase of phosphorylated HSL (p-HSL) protein and a rising tendency of adipose triglyceride lipase (ATGL) protein relative to those of the DEX group. For lipid anabolism, fatty acid synthase (FAS) and adiponectin protein expression in visceral fat rose notably in ZAG KO mice after DEX treatment. In conclusion, ZAG knockout can affect the gene expression profile of adipose tissue, reduce elevated TG and NEFA levels in plasma, and alter lipid metabolism under DEX treatment. These findings provide new insights into the mechanism of lipid metabolic disorders in response to stress.

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