Gene expression of paired abdominal adipose AQP7 and liver AQP9 in patients with morbid obesity

Unitat de Recerca, Hospital Universitari de Tarragona Joan XXIII, IISPV, 43007 Tarragona, Spain.
Metabolism: clinical and experimental (Impact Factor: 3.89). 08/2009; 58(12):1762-8. DOI: 10.1016/j.metabol.2009.06.004
Source: PubMed


The trafficking of glycerol from adipose and hepatic tissue is mainly mediated by 2 aquaporin channel proteins: AQP7 and AQP9, respectively. In rodents, both aquaporins were found to act in a coordinated manner. The aim was to study the relationship between adipose AQP7 and hepatic AQP9 messenger RNA expression and the presence of glucose abnormalities simultaneously in morbid obesity. Adipose tissue (subcutaneous [SAT] and visceral [VAT]) and liver biopsies from the same patient were obtained during bariatric surgery in 30 (21 male and 9 female) morbidly obese subjects. Real-time quantification of AQP7 in SAT and VAT and hepatic AQP9 gene expression were performed. A 75-g oral glucose tolerance test was performed in all subjects. The homeostasis model assessment of insulin resistance and lipidic profile were also determined. Visceral adipose tissue AQP7 expression levels were significantly higher than SAT AQP7 (P = .009). Subcutaneous adipose tissue AQP7 positively correlated with both VAT AQP7 and hepatic AQP9 messenger RNA expression (r = 0.44, P = .013 and r = 0.45, P = .012, respectively). The correlation between SAT AQP7 and liver AQP9 was stronger in intolerant and type 2 diabetes mellitus subjects (r = 0.602, P = .011). We have found no differences in compartmental AQP7 adipose tissue distribution or AQP9 hepatic gene expression according to glucose tolerance classification. The present study provides, for the first time, evidence of coordinated regulation between adipose aquaglyceroporins, with a greater expression found in visceral fat, and between subcutaneous adipose AQP7 and hepatic AQP9 gene expression within the context of human morbid obesity.


Available from: Matilde R Chacon, Dec 10, 2014
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    • "A downregulated AQP7 expression could then be involved in obesity susceptibility by reducing glycerol release and by promoting the accumulation of lipids in subcutaneous adipose tissue [31]. Studies also suggested that AQP7 expression is higher in visceral adipose tissue from obese subjects, compared with subcutaneous, in agreement with the fact that visceral adipose tissue is more metabolically active (higher lipolytic capability) than subcutaneous (higher fat accumulation) [35,36]. Therefore, in the present study, palmitate-induced TG accumulation in adipocytes may be associated with a decreased AQP7 expression. "
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    ABSTRACT: Background Adipocyte-secreted apelin contributes to decreased adiposity and to improved insulin resistance, but the mechanisms remain unknown. The present study aimed to assess if apelin-13 is an upstream signal regulation factor of aquaporin 7 (AQP7), a water-glycerol transporter present in the plasma membrane of adipocytes that plays a key role in the regulation of lipid accumulation. Material/Methods 3T3-L1 pre-adipocytes were induced to fully differentiated adipocytes; hypertrophic adipocytes were then induced using palmitate. The effects of apelin-13 on AQP7 expression in hypertrophic adipocytes were investigated before and after treatment with LY249002, a PI3K inhibitor. Accumulation of cytoplasmic triglycerides (TG) in hypertrophic adipocytes was also determined. Results We found that 0.1 mM of palmitate induced a model of hypertrophic adipocytes with a lower AQP7 expression (0.26±0.07 vs. 0.46±0.04, P<0.05). Apelin-13 100 nM or 1000 nM upregulated AQP7 mRNA expression (100 nM: 0.54±0.06 and 1000 nM: 0.58±0.09 vs. control: 0.33±0.04, both P<0.05), and decreased accumulation of cytoplasmic triglycerides in hypertrophic adipocytes. Pretreatment using 10 μM LY294002 prevented the increase in AQP7 expression observed when using apelin-13 alone (apelin-13 + LY49002: 0.38±0.03 vs. apelin-13: 0.54±0.06, P<0.05), as well as the decreased cytoplasmic TG accumulation (apelin-13 + LY294002: 3.79±0.04 μM per μg/ml vs. apelin-13: 3.32±0.08 μM per μg/ml, P<0.05). Conclusions Apelin-13 decreases lipid storage in hypertrophic adipocytes in vitro, possibly through the upregulation of AQP7 expression by the PI3K signaling pathway. Treatment using apelin-13 and AQP modulators might represent novel treatment strategies against obesity and its related complications.
    Medical science monitor: international medical journal of experimental and clinical research 08/2014; 20:1345-52. DOI:10.12659/MSM.890124 · 1.43 Impact Factor
    • "AQP7 aquaporin-7 facilitates water, glycerol and urea transport; forms a channel for water and glycerol 7 (18) glucose abnormalities [111]; glycerol metabolism and metabolic syndrome [112]; atherosclerosis [113] PTPN14 tyrosine-protein phosphatase non-receptor type 14 protein tyrosine phosphatase activity; regulate cellular processes cell growth, differentiation, mitotic cycle, and oncogenic transformation 7 (15) attention deficit hyperactivity disorder [114]; cancer [115] KIR2DL3 killer cell immunoglobulin-like receptor 2DL3 antigen binding; regulation of immune response 7 (11) multiple sclerosis [116] PRIM2 DNA primase large subunit DNA binding; DNA replication 7 (11) Cancer [117] HEATR1 HEAT repeat-containing protein 1 ribosome biosynthesis; nucleolar processing of pre-18S ribosomal RNA 7 (10) HMCN1 hemicentin-1 vision; sensory transduction 7 (8) macular degeneration [118]; diabetic nephropathy [119] CSMD1 CUB and sushi domain-containing protein 1 regulator of inflammation in developing CNS; neuronal growth cone function 7 (7) AD [82]; schizophrenia [120] [121]; multiple sclerosis [122], Parkinson's disease [123]; cancer [124] [125] NEB nebulin muscle cytoskeletal component 6 (12) nemaline myopathy [126] TPTE putative tyrosine-protein phosphatase TPTE unknown 6 (11) Robertsonian Down syndrome[42] SVIL supervillin cytoskeleton organization; cell adhesion; skeletal muscle development PTK2B protein-tyrosine kinase 2-beta reorganization of the actin cytoskeleton; cell polarization;, cell migration; adhesion; spreading and bone remodeling 6 (8) major depressive disorder [128] "
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    ABSTRACT: Background: Although genome-wide association studies have shown that genetic factors increase the risk of suffering late-onset, sporadic Alzheimer's disease (SAD), the molecular mechanisms responsible remain largely unknown. Objective: The aim of the study was to investigate the presence of somatic, brain-specific single nucleotide variations (SNV) in the hippocampus of SAD samples. Methods: By using bioinfiormatic tools, we compared whole exome sequences in paired blood and hippocampal genomic DNAs from 17 SAD patients and from 2 controls and 2 vascular dementia patients. Results: We found a remarkable number of SNVs in SAD brains (~575 per patient) that were not detected in blood. Loci with hippocampus-specific (hs)-SNVs were common to several patients, with 38 genes being present in 6 or more patients out of the 17. While some of these SNVs were in genes previously related to SAD (e.g., CSMD1, LRP2), most hs-SNVs occurred in loci previously unrelated to SAD. The most frequent genes with hs-SNVs were associated with neurotransmission, DNA metabolism, neuronal transport, and muscular function. Interestingly, 19 recurrent hs-SNVs were common to 3 SAD patients. Repetitive loci or hs-SNVs were underrepresented in the hippocampus of control or vascular dementia donors, or in the cerebellum of SAD patients. Conclusion: Our data suggest that adult blood and brain have different DNA genomic variations, and that somatic genetic mosaicism and brain-specific genome reshaping may contribute to SAD pathogenesis and cognitive differences between individuals.
    Journal of Alzheimer's disease: JAD 07/2014; 42(4). DOI:10.3233/JAD-140891 · 4.15 Impact Factor
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    • "As a member of the aquaglyceroporin family, AQP9 is abundantly expressed on the sinusoid surface of hepatocytes, indicating that AQP9 is involved in the liver-blood glycerol exchange (21). Additionally, certain studies have suggested that AQP9 is involved in hepatocyte lipid metabolism and steatosis (22–24). Apart from its contribution to neoplasm pathogenesis, AQP9 has also been implicated in the process of inflammation; a previous study indicated that a strong increase in AQP9 transcripts was observed in synovial tissues from patients with osteoarthritis and rheumatoid arthritis (25). "
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    ABSTRACT: Aquaglyceroporin 9 (AQP9) is considered to be involved in numerous types of carcinogenic processes, particularly in liver carcinoma. AQP9 expression is significantly decreased in the human hepatocellular carcinoma when compared with the non-tumourigenic liver, which leads to increased resistance to apoptosis. In addition, AQP9 is permeable to glycerol and urea. The involvement of AQP9 in leukemia has not been fully delineated. It is proposed that abnormal proliferation of hematopoietic stem cells (HSCs) contributes to leukemia carcinogenesis. Therefore, the present study aimed to investigate the possible roles of AQP9 in HSCs and its effect on the intracellular glycerol content. HSCs and non-HSCs (nHSCs) were isolated via magnetic-activated cell sorting and then subjected to flow cytometry for evaluation of purity. White blood cells (WBCs) were isolated from peripheral blood from healthy volunteers. Furthermore, AQP9 expression was examined at the mRNA and protein levels using western blotting and reverse transcription-polymerase chain reaction (RT-PCR). The glycerol content of HSCs, nHSCs and WBCs was evaluated by ELISA. Finally, in order to observe the morphology of HSCs and nHSCs, a blood smear was conducted and the cells were observed with Wright-Giemsa staining. The results indicated that the glycerol content in the HSCs was markedly greater than that in the nHSCs. AQP9 mRNA and protein expression was not detected in the HSCs and nHSCs, but was identified in the WBCs. Moreover, the HSC morphological characteristics included round or oval cells with round, slightly oval or irregularly shaped nuclei. Additionally, the nuclei occupied almost the entire cell, were located in the middle or were biased toward one side, and were stained light purple or red. Overall, our results indicated that intracellular glycerol is involved in HSC proliferation, despite the fact that glycerol is not mediated by AQP9. Hence, our findings may be useful in further understanding the mechanism of leukemia carcinogenesis, and these data may be valuable in developing future therapeutic strategies.
    Oncology letters 07/2014; 8(1):169-174. DOI:10.3892/ol.2014.2142 · 1.55 Impact Factor
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