Aquaporin 7 Research Articles

Glycerol Handling in Paired Visceral and Subcutaneous Adipose Tissues in Women with Normal Weight and Upper-Body Obesity.

In adipose tissue, reduced expression of the glycerol channel aquaporin 7 (AQP7) has been associated with increased accumulation of triglyceride. The present study determines the relative protein abundances of lipolytic enzymes, AQP7, and cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in paired mesenteric and omental visceral adipose tissue (VAT) and abdominal and femoral subcutaneous adipose tissue (SAT) in women with either normal weight or upper-body obesity. No differences in the expression of hormone-sensitive lipase (HSL) or AQP7 were found between the two groups in the four depots. The expression of adipocyte triglyceride lipase (ATGL) and HSL were higher in omental VAT and femoral SAT than in mesenteric VAT in both groups of women. Similarly, AQP7 expression was higher in omental VAT than in mesenteric VAT. The expression of PEPCK-C was lower in omental VAT than in femoral SAT. No correlation between the expression of AQP7 and the mean adipocyte size was observed; however, the expression of PEPCK-C positively correlated with the mean adipocyte size. In conclusion, a depot-specific protein expression pattern was found for ATGL, HSL, AQP7, and PEPCK-C. The expression pattern supports that the regulation of AQP7 protein expression is at least in part linked to the lipolytic rate. Furthermore, the results support that the synthesis of glycerol-3-phosphate via glyceroneogenesis contributes to regulating triglyceride accumulation in white adipose tissue in women.

Association between Aquaporin 7 Expression and Myocardial Protection with Nicorandil or Del Nido Cardioplegia: An Experimental Study

Background: Aquaporin 7 (AQP7), a member the aquaglyceroporin subgroup of the AQP family, is a water channel that controls transport of glycerol and water in heart tissues. It facilitates the uptake of glycerol, a substrate for cardiac energy production, in cardiomyocytes. St. Thomas' Hospital cardioplegic solution No. 2 has cardio-protective effect even in AQP7-deficient hearts. Here, we aimed to determine whether nicorandil or del Nido cardioplegia (DNC) solution can protect AQP7-deficient hearts. Methods: The hearts of male AQP7 knockout (KO) and wild-type (WT) C57/B6N mice (age >15 weeks) were aerobically perfused using the Langendorff technique, and cardiac function was measured as left ventricular diastolic pressure (LVDP) throughout the study. Troponin T was measured as an indicator of myocardial damage after reperfusion for 60 min. We compared WT and KO controls subjected to 25 min of global ischemia as well as WT and KO groups infused with nicorandil (100 µM) for 10 min followed by 25 min of global ischemia. We also compared WT-DNC and KO-DNC hearts administered with DNC for 2 min followed by 23 min of global ischemia (Study 2). Results: The final recovery rates of LVDP were 20.8 ± 7.0%, 28.1 ± 7.6%, 40.0 ± 8.4%, and 38.7 ± 4.7% in the WT control, KO control, WT nicorandil, and KO nicorandil groups, respectively. The LVDP recovered faster in the hearts treated with DNC and reached a significantly higher plateau in the KO than in the WT hearts. Troponin T values were 2144 ± 493 and 1313 ± 717 in the WT and KO groups, respectively (p = 0.041). Conclusion: The Langendorff perfusion model revealed similar myocardial protective effects of nicorandil in AQP7-deficient mice as in WT mice. AQP7 deficiency did not impair the cardioprotective effects of DNC solution.

Therapeutic effects of intermittent fasting on high-fat, high-fructose diet; involvement of jejunal aquaporin 1, 3, and 7

BackgroundAquaporins (AQPs) are transmembrane channel proteins. Aquaporin 1 (AQP1), Aquaporin 3 (AQP3), and Aquaporin 7 (AQP7) are expressed in the jejunum. The purpose of this study was to ascertain how a high-fat high-fructose diet (HFFD) and intermittent fasting (IF) affect AQP1, AQP3, and AQP7 expression in the rat jejunum. MethodsSixteen adult male rats were divided into control rats (n = 4) fed on a basal diet and water ad libitum for 12 weeks; IF control rats (n = 4) followed the IF protocol, HFFD-fed rats (n = 8) fed HFFD for eight weeks, and rats were randomized into two groups: HFFD only or HFFD and IF protocol from the beginning of the 9th week until the end of the experiment. The lipid profile values were assessed after 12 weeks. Jejunal oxidative markers (malondialdehyde and reduced glutathione) and AQP1, AQP3, and AQP7 mRNA expression were measured. Jejunal sections were used for morphometric analysis of villus length and crypt depth. Immunohistochemical evaluation of AQP1, AQP3, and AQP7 expression was also performed. ResultsIF ameliorates HFFD-induced lipid profile, oxidative stress, and jejunal morphometric changes. The results of both mRNA expression using PCR and immunohistochemistry showed a significant increase in AQP1, AQP3, and AQP7 expression in HFFD, whereas IF caused a decline in this expression. ConclusionThese findings suggest that IF can reduce inflammation, and oxidative stress and restore jejunal morphology caused by HFFD.

Prognostic values and immune infiltration of KLF15, AQP7, AGPAT9 in glioma and glioblastoma

BackgroundsThe overall survival of patients with lower-grade gliomas and glioblastoma varies greatly. No reliable or existing procedures can accurately forecast survival and prognostic biomarkers for early diagnosis in glioma and glioblastoma. However, investigations are progressing in immunotherapy, tumor purity, and tumor microenvironment which may be therapeutic targets for glioma and glioblastoma.ResultsThis study indicated the possible prognostic signatures that can be used to identify immune-related prognostic biomarkers in the prediction of the survival of low-grade glioma (LGG) patients which may be a possible therapeutic target. In addition, the Kaplan–Meier plot, ESTIMATE algorithm, and TIMER 2.0 analysis indicated that Krüppel-like factor 15 (KLF15) p = 0.030, Aquaporin 7 (AQP7) p = 0.001, and Human 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) p = 0.005 are significantly associated in glioma. Hence, they may be possible prognostic biomarkers in glioma. Meanwhile, in the glioblastoma, only KLF15 has a significant association with glioblastoma (p = 0.025). Stromal and immune scores of gliomas were determined from transcriptomic profiles of LGG cohort from TCGA (The Cancer Genome Atlas) using the ESTIMATE (Estimation of Stromal and Immune cells in Malignant Tumours using Expression data algorithm). The immune infiltration of the KLF15, AQP7, and AGPAT9 for low-grade glioma and glioblastoma was determined using TIMER immune 2.0 which indicates correlation with tumor purity for KLF15, AQP7, and AGPAT9, but only KLF15 and AGPAT9 are significantly associated in both glioma and glioblastoma, respectively.ConclusionsThese results highlight the significance of microenvironment monitoring, analysis of glioma and glioblastoma prognosis, and targeted immunotherapy. To our knowledge, this is the first time to investigate an analysis that revealed that KLF15, AQP7, and AGPAT9 may be important prognostic biomarkers for patients with glioma and KLF15 for patients with glioblastoma. Meanwhile, KLF15 and AGPAT9 are significantly associated in both glioma and glioblastoma, respectively, for tumor purity.

Time-dependent laxative effect of sennoside A, the core functional component of rhubarb, is attributed to gut microbiota and aquaporins.

Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance. This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs). Based on a mouse constipation model, 2.6mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image. Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the administration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus, Romboutsia, Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The comprehensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration. Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia, Akkermansia and UCG_005 and water channels of AQP1 and AQP3.

Morphological and Molecular Investigations of Aquaporin-7 (AQP-7) in Male Camelus dromedarius Reproductive Organs

Aquaporins (AQP) are involved in bidirectional transfers of water and small solutes across cell membranes. They are present in all tissues. However, the expression of AQP-7 has not yet been demonstrated in the reproductive tract of the camelid Camelus dromedarius. The study presented here concerns the immunohistochemical evidence of aquaporin-7 (AQP-7) in different parts of the male genital tract of Camelus dromedarius. To check the immune reactivity levels of anti-AQP-7 antibody in the male genital tract of Camelus dromedarius, the testes (proximal part, distal part and rete testis), epididymis (head, body and tail), ductus deferens (initial, middle and ampullary part) and prostate gland (compact and disseminated part) were collected from 12 male camels during the rutting and non-rutting seasons and subjected to immunohistochemistry. The result showed that the highest level of AQP-7 mRNA expression was in the testis of rutting and non-rutting males compared to the ductus deferens, epididymis and prostate. In addition, the highest mRNA gene expression of AQP-7 was in rutting males compared to non-rutting males. AQP-7 mRNA expression was higher in the ret testis, the body of the epididymis, the ampullary part of the ductus deferens and the compact part of the prostate. The immune reactivity levels of AQP-7 in rutting males showed strong reactivity in the testis and prostate compared to the epididymis and ductus deferens. On the basis of the results, it can be concluded that the distribution of the AQP-7 transcript and protein varied among rutting and non-rutting seasons and that the physiological roles of AQP-7 in the transportation of lipids, energy and water should be considered the main challenge in the activity and establishment of male Camelus dromedarius fertility during the rutting and non-rutting seasons. Moreover, AQP-7 detection is critical in assessing regulation and screening for new modulators that can prompt the development of effective medication to enhance fertility during rutting and non-rutting seasons.

WGCNA combined with machine learning algorithms for analyzing key genes and immune cell infiltration in heart failure due to ischemic cardiomyopathy.

Ischemic cardiomyopathy (ICM) induced heart failure (HF) is one of the most common causes of death worldwide. This study aimed to find candidate genes for ICM-HF and to identify relevant biomarkers by machine learning (ML). The expression data of ICM-HF and normal samples were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between ICM-HF and normal group were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and gene ontology (GO) annotation analysis, protein-protein interaction (PPI) network, gene pathway enrichment analysis (GSEA), and single-sample gene set enrichment analysis (ssGSEA) were performed. Weighted gene co-expression network analysis (WGCNA) was applied to screen for disease-associated modules, and relevant genes were derived using four ML algorithms. The diagnostic values of candidate genes were assessed using receiver operating characteristic (ROC) curves. The immune cell infiltration analysis was performed between the ICM-HF and normal group. Validation was performed using another gene set. A total of 313 DEGs were identified between ICM-HF and normal group of GSE57345, which were mainly enriched in biological processes and pathways related to cell cycle regulation, lipid metabolism pathways, immune response pathways, and intrinsic organelle damage regulation. GSEA results showed positive correlations with pathways such as cholesterol metabolism in the ICM-HF group compared to normal group and lipid metabolism in adipocytes. GSEA results also showed a positive correlation with pathways such as cholesterol metabolism and a negative correlation with pathways such as lipolytic presentation in adipocytes compared to normal group. Combining multiple ML and cytohubba algorithms yielded 11 relevant genes. After validation using the GSE42955 validation sets, the 7 genes obtained by the machine learning algorithm were well verified. The immune cell infiltration analysis showed significant differences in mast cells, plasma cells, naive B cells, and NK cells. Combined analysis using WGCNA and ML identified coiled-coil-helix-coiled-coil-helix domain containing 4 (CHCHD4), transmembrane protein 53 (TMEM53), acid phosphatase 3 (ACPP), aminoadipate-semialdehyde dehydrogenase (AASDH), purinergic receptor P2Y1 (P2RY1), caspase 3 (CASP3) and aquaporin 7 (AQP7) as potential biomarkers of ICM-HF. ICM-HF may be closely related to pathways such as mitochondrial damage and disorders of lipid metabolism, while the infiltration of multiple immune cells was identified to play a critical role in the progression of the disease.

Increased Aquaporin-7 Expression Is Associated with Changes in Rat Brown Adipose Tissue Whitening in Obesity: Impact of Cold Exposure and Bariatric Surgery

Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in adipocytes, in the improvement of brown adipose tissue (BAT) whitening, a process whereby brown adipocytes differentiate into white-like unilocular cells, after cold exposure or bariatric surgery in male Wistar rats with diet-induced obesity (DIO) (n = 229). DIO promoted BAT whitening, evidenced by increased BAT hypertrophy, steatosis and upregulation of the lipogenic factors Pparg2, Mogat2 and Dgat1. AQP7 was detected in BAT capillary endothelial cells and brown adipocytes, and its expression was upregulated by DIO. Interestingly, AQP7 gene and protein expressions were downregulated after cold exposure (4 °C) for 1 week or one month after sleeve gastrectomy in parallel to the improvement of BAT whitening. Moreover, Aqp7 mRNA expression was positively associated with transcripts of the lipogenic factors Pparg2, Mogat2 and Dgat1 and regulated by lipogenic (ghrelin) and lipolytic (isoproterenol and leptin) signals. Together, the upregulation of AQP7 in DIO might contribute to glycerol influx used for triacylglycerol synthesis in brown adipocytes, and hence, BAT whitening. This process is reversible by cold exposure and bariatric surgery, thereby suggesting the potential of targeting BAT AQP7 as an anti-obesity therapy.

Aquaporin 7 is upregulated through the PI3K-Akt pathway and modulates decidualisation of endometrial stromal cells.

Aquaporin 7 (AQP7) is selectively expressed in decidualised endometrial stromal cells (ESCs) of mice surrounding the embryonic implantation sites. However, the roles of AQP7 and the underlying mechanism that regulates AQP7 expression in endometrial decidualisation after implantation are still unclear. This study aimed to investigate the role of the PI3K-Akt pathway in regulating the expression of AQP7 in ESCs and decidualisation. Primary ESCs of pregnant mice were isolated to establish in vitro decidualisation models. PI3K inhibitor LY294002 was added to the decidualisation models, then AQP7 expression, changes in decidualised ESC morphology and expression of decidualisation marker molecules were examined. AQP7 knockdown reduced the proliferation and differentiation of ESCs with in vitro induced decidualisation. Furthermore, when the activity of PI3K was inhibited by LY294002, the expression of AQP7 in decidualised ESCs was decreased and both the proliferation and differentiation of ESCs were significantly reduced. This indicates that AQP7 is a key molecule involved in endometrial decidualisation and the expression of AQP7 is upregulated through activation of the PI3K-Akt pathways, which promotes the proliferation and differentiation of the ESCs, thus affecting occurrence of decidualisation. This study may provide a new biomarker for the diagnosis of infertility and a new drug target for the prevention and treatment of infertility.

Biochemical and molecular study on pigment epithelium derived factor and aquaporin channel protein 7 gene expression in obese children

Background and aimGenetic variables have a crucial function in the onset of pediatric obesity. PEDF was implicated in the development of obesity, also the transmembrane channel aquaporin 7 (AQP7), has been demonstrated to be involved in obesity and its complications. We aimed to study the association of the expression level of pigment epithelium-derived factor (PEDF) and aquaporin channel protein 7 (AQP7) genes with the obesity risk in Egyptian children and to correlate it with clinicopathological features in patients. Subjects and methodsThis study was conducted in the period between December 2020 to June 2021. A total of 150 individuals were divided into two groups: Group 1 enrolled 75 children with obesity and 75 healthy controls were involved in this study. PEDF (SERPINF1) and AQP7 gens mRNA expressions were analyzed by the real-time quantitative polymerase chain reaction (qPCR) technique. ResultsThe expression level of PEDF was increased while that for AQP7 was decreased in obese group when compared with the control group. Also, there was a positive correlation between PEDF and serum triglyceride level while AQP7 showed a positive correlation with serum HDL (mg/dl) and a negative correlation with age. ConclusionElevated expression of PEDF and reduced expression of AQP7 in obese children have a key role in the progression of obesity and the pathogenesis of insulin resistance.

IMPACT OF AQUAPORIN-3, AQUAPORIN-7 AND HEPARANASE GENETIC POLYMORPHISMS ON AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PROGRESSION

Objective: Autosomal Dominant Polycystic Kidney Disease(ADPKD) is a monogenic disease characterized by the growth of cysts in the kidneys, which can progress to end-stage renal disease(ESRD). However, this progression is heterogeneous. Aquaporin-3(AQP3) and Aquaporin-7(AQP7) are water channels involved in the inflammatory response and proliferation, expressed in the kidney and may have a role in cyst epithelial proliferation. Heparanase(HPSE) is an enzyme that cleaves heparan sulfate side chains of proteoglycans and has an increased expression in the glomerulus in diseases associated with proteinuria. This study aims to evaluate the impact of AQP3, AQP7 and HPSE genetic polymorphisms and some biomarkers related to cardiovascular risk in ESRD progression in patients with ADPKD. Design and method: 95 ADPKD(52.6% females), mean age 44.78 ± 14.34 years were diagnosed and had follow-up> 60 months. Variation values of serum creatinine(SCr) were used to stratify patients into fast progressors(FP) and slow progressors. Biochemical parameters and genetic polymorphisms were determined by standardized methods and endpoint analysis, respectively. Statistical analysis was performed using SPSS software considering p-value < 0.05. Results: For HPSE, genotype AA was associated with increased risk for FP in CKD(p = 0.027), while allele G was associated with high values of SCr(p = 0.010). A trend was observed in genotype CC of AQP7 with higher SCr(p = 0.066). No associations were found between AQP3 polymorphism and progression in ADPKD. The increased levels of: creatinine(SCr), albumin creatinine ratio(Alb/Cr), microalbumin(mAlb) and parathyroid hormone(PTH) were associated with the FP and stage 4 and 5 of chronic kidney disease(CKD). The opposite occurred in hemoglobin(Hb) levels and the product of calcium and phosphorus. No associations were found between AQP3 polymorphism and progression in ADPKD. Higher values of SCr were found in genotype CC of AQP3(p = 0.016) and a trend in allele T of AQP7(p = 0.070) and genotype AA of HPSE(p = 0.056). PTH was higher in genotype CC of AQP3(p = 0.047). AQP7 polymorphism was associated with elevated values of:Alb/Scr(p = 0.021) in allele T, calcium(p = 0.003) in genotype TT and Hb(p = 0.012) in allele C. Conclusions: The studied polymorphisms seem to directly impact and/or modulate levels of some biomarkers associated with progression and stage of CKD in ADPKD patients.

Cholecystokinin promotes functional expression of the aquaglycerol channel aquaporin 7 in adipocytes.

Cholecystokinin (CCK) promotes triglyceride storage and adiponectin production in white adipose tissue (WAT), suggesting that CCK modulates WAT homeostasis. Our goal was to investigate the role of CCK in regulating the expression and function of the aquaglycerol channel aquaporin 7 (AQP7), a protein that is pivotal for maintaining adipocyte homeostasis and preserving insulin responsiveness. The effect of the bioactive fragment of CCK, CCK-8, in regulating adipose AQP7 expression and glycerol efflux was assessed in rats as well as in preadipocytes. Moreover, the involvement of insulin receptors in the effects of CCK-8 was characterized in preadipocytes lacking insulin receptors. CCK-8 induced AQP7 gene expression in rat WAT, concomitantly increasing plasma glycerol concentration. In isolated preadipocytes, CCK-8 also enhanced both AQP7 expression and glycerol leakage. The effects of CCK-8 were independent of the lipolysis rate, as CCK-8 failed to promote fatty acid release by adipocytes. In addition, CCK-8 did not enhance hormone sensitive lipase phosphorylation, which is the rate-limiting step of lipolysis. Moreover, the effects of CCK-8 were dependent on the activation of protein kinase B and PPARγ. Silencing insulin receptor expression inhibited CCK-8-induced Aqp7 expression in preadipocytes. Furthermore, insulin enhanced the effect of CCK-8. CCK regulates AQP7 expression and function, and this effect is dependent on insulin. Accordingly, CCK receptor agonists could be suitable for preserving and improving insulin responsiveness in WAT.

Association study of single nucleotide polymorphisms of AQP7 and AQP9 genes with type 2 diabetes mellitus among ethnic Han Chinese population

To assess the association of single nucleotide polymorphisms (SNP) of aquaporin 7 ( AQP7) and aquaporin 9 ( AQP9) genes and type 2 diabetes mellitus (T2DM) among ethnic Han Chinese population. A case-control study involving 1194 subjects with T2DM and 1274 non-diabetic mellitus (NDM) subjects were enrolled. Genotypes of three SNPs (rs3758269 of AQP7 gene, rs16939881 and rs57139208 of AQP9 gene) were determined by using a MassArray method. The association of the three SNPs with T2DM was assess, and the correlation of glucose and lipid metabolism parameters with various SNP genotypes in the NDM group was analyzed. The allelic and genotypic frequencies of the three SNPs did not differ significantly between the two groups (P>0.05). Nor was there significant difference between the two groups with different genetic models (P>0.05). No significant association of genotypes of AQP7 gene rs3758269, AQP9 gene rs16939881 and rs57139208 with glucose and lipid metabolism parameters were observed in the NDM group (P>0.05). The rs3758269 in AQP7 gene and rs16939881 and rs57139208 in AQP9 gene are not associated with the genetic susceptibility of T2DM among ethnic Han Chinese population.

Development of an Orthotopic Pancreatic Ductal Adenocarcinoma (PDAC) Patient Derived Xenografts (PDX) Preclinical Model and Characterization of Aquaporin 7 (AQP7) Expression

Introduction: Pancreatic cancer is a frequent malignancy associated with poor prognosis. Orthotopic patient-derived xenografts (PDX) represent the cutting edge of translational cancer research in the field of precision medicine. Here, we report the establishment of an orthotopic PDX model of pancreatic ductal adenocarcinoma (PDAC) for the development of novel therapeutic approaches. Method: Tumor samples were collected upon surgery and inoculated into immunocompromised mice. After xenograft development, tumors were compared to patient's original tumor by immunochemistry, cultured and serially transplanted into mice for the determination of tumor growth characteristics. Aquaporin 7 (AQP7) protein expression was studied using Western Blot and immunochemistry. Stem cell characteristics were examined by flow cytometry and limited dilution method. Moreover, activity of selected compounds was studied both in vitro and in vivo. Results: 20 out of 24 engraftments (83.3%) from tissue collected from five patients were successful. Immunohistochemical analysis of representative tumors revealed that they represent the most aggressive and less differentiated population of the patient's tumor. In vitro studies to characterize the expression of AQP7 expression showed that AQP7 is under-expressed in pancreatic cancer. Further in vivo studies to evaluate the activity of AQP7 as single agents or in combination with established drugs are ongoing. Conclusion: These findings uncover the great potential role of PDX for precision medicine and drug discovery, along with the implication of AQP7 in PDAC biology.

Identificación del polimorfismo aquaporin 7 Gene y fertilidad in vivo de búfalos en Egipto

This work aimed to investigate the genetic polymorphism of Aquaporin 7 (AQP7) gene and its association with the in-vivo fertility of Egyptian buffalo bulls. A total of 188 fresh semen ejaculates were collected from 47 buffalo bulls and subjected to semen evaluation. The bulls were grouped according to in-vivo fertility relying on sire conception rate (SCR) into high (SCR>50%, n=41) and low (SCR<50%, n=6) fertile bulls. DNA was extracted from semen and a 200 bp fragment of the AQP7 gene was amplified by PCR. The genetic polymorphism of AQP7 gene was detected by restriction fragment length polymorphism, the single strand conformation polymorphism and the nucleotide sequencing. The results revealed that SCR was significantly (p<0.001) increased in high (71.4±1.3) than low (44.7±2.8) fertile bulls while the ejaculate volume, individual motility%, lives sperm%, sperm concentration and sperm abnormalities showed a non-significant difference in both groups. The AQP7 gene showed no genetic variation in all bulls. The alignment of the resultant sequence with buffalo AQP7 gene sequence (ID: XM_006066699.2) showed 100% identity (122/122), however, deletion of A49 was discovered when the sequence was aligned with ID: XM_006066700.2 of buffalo in GenBank. In conclusion, the sire conception rate is not associated with any genetic variation in Aquaporin 7 gene. The Aquaporin 7 gene could be a highly conserved sequence in Egyptian buffalo bulls. Future research on large herd populations in different regions of AQP7 gene is required for evaluating the AQP7 gene polymorphism and its association with the fertility of Egyptian buffalo bulls.

LPL/AQP7/GPD2 promotes glycerol metabolism under hypoxia and prevents cardiac dysfunction during ischemia.

In the heart, fatty acid is a major energy substrate to fuel contraction under aerobic conditions. Ischemia downregulates fatty acid metabolism to adapt to the limited oxygen supply, making glucose the preferred substrate. However, the mechanism underlying the myocardial metabolic shift during ischemia remains unknown. Here, we show that lipoprotein lipase (LPL) expression in cardiomyocytes, a principal enzyme that converts triglycerides to free fatty acids and glycerol, increases during myocardial infarction (MI). Cardiomyocyte-specific LPL deficiency enhanced cardiac dysfunction and apoptosis following MI. Deficiency of aquaporin 7 (AQP7), a glycerol channel in cardiomyocytes, increased the myocardial infarct size and apoptosis in response to ischemia. Ischemic conditions activated glycerol-3-phosphate dehydrogenase 2 (GPD2), which converts glycerol-3-phosphate into dihydroxyacetone phosphate to facilitate adenosine triphosphate (ATP) synthesis from glycerol. Conversely, GPD2 deficiency exacerbated cardiac dysfunction after acute MI. Moreover, cardiomyocyte-specific LPL deficiency suppressed the effectiveness of peroxisome proliferator-activated receptor alpha (PPARα) agonist treatment for MI-induced cardiac dysfunction. These results suggest that LPL/AQP7/GPD2-mediated glycerol metabolism plays an important role in preventing myocardial ischemia-related damage.

Pre-Weaning Inulin Supplementation Alters the Ileal Transcriptome in Pigs Regarding Lipid Metabolism.

Prebiotics, such as inulin, are non-digestible compounds that stimulate the growth of beneficial microbiota, which results in improved gut and overall health. In this study, we were interested to see if, and how, the ileal transcriptome altered after inulin administration in the pre-weaning period in pigs. Seventy-two Piétrain–Landrace newborn piglets were divided into three groups: (a) a control (CON) group (n = 24), (b) an inulin (IN)-0.5 group (n = 24), and (c) an IN-0.75 group (n = 24). Inulin was provided as a solution and administered twice a day. At week 4, eight piglets per group, those closest to the average in body weight, were sacrificed, and ileal scrapings were collected and analyzed using 3′ mRNA massively parallel sequencing. Only minor differences were found, and three genes were differentially expressed between the CON and IN-0.5 group, at an FDR of 10%. All three genes were downregulated in the IN-0.5 group. When comparing the CON group with the IN-0.75 group, five genes were downregulated in the IN-0.75 group, including the three genes seen earlier as differentially expressed between CON and IN-0.5. No genes were found to be differential expressed between IN-0.5 and IN-0.75. Validation of a selection of these genes was done using qRT-PCR. Among the downregulated genes were Angiopoietin-like protein 4 (ANGPTL4), Aquaporin 7 (AQP7), and Apolipoprotein A1 (APOA1). Thus, although only a few genes were found to be differentially expressed, several of them were involved in lipid metabolism, belonging to the peroxisome proliferator-activated receptor (PPAR) signaling pathway and known to promote lipolysis. We, therefore, conclude that these lipid metabolism genes expressed in the ileum may play an important role when supplementing piglets with inulin early in life, before weaning.

Metformin inhibits MAPK signaling and rescues pancreatic aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus

Metformin is the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. Although accumulated evidence has shed light on the consequences of metformin action, the precise mechanisms of its action, especially in the pancreas, are not fully understood. Aquaporin 7 (AQP7) acts as a critical regulator of intraislet glycerol content, which is necessary for insulin production and secretion. The aim of this study was to investigate the effects of different doses of metformin on AQP7 expression and explore the possible mechanism of its protective effects in the pancreatic islets. We used an in vivo model of high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic β-cells (INS-1 cells) damaged by hyperglycemia and hyperlipidemia. Our data showed that AQP7 expression levels were decreased, whereas p38 and JNK mitogen-activated protein kinases (MAPKs) were activated in vivo and in vitro in response to hyperglycemia and hyperlipidemia. T2DM rats treated with metformin demonstrated a reduction in blood glucose levels and increased regeneration of pancreatic β-cells. In addition, metformin upregulated AQP7 expression as well as inhibited activation of p38 and JNK MAPKs both in vivo and in vitro. Overexpression of AQP7 increased glycerol influx into INS-1 cells, whereas inhibition of AQP7 reduced glycerol influx, thereby decreasing subsequent insulin secretion. Our findings demonstrate a new mechanism by which metformin suppresses the p38 and JNK pathways, thereby upregulating pancreatic AQP7 expression and promoting glycerol influx into pancreatic β-cells and subsequent insulin secretion in T2DM.

Feprazone Displays Antiadipogenesis and Antiobesity Capacities in in Vitro 3 T3-L1 Cells and in Vivo Mice

Background and purpose: Excessive lipid accumulation in adipose tissues and deregulation of adipogenesis-induced obesity affect millions of people worldwide. Feprazone, a nonsteroidal anti-inflammatory drug, has a wide clinical use. However, it is unknown whether Feprazone possesses an antiadipogenic ability. The aim of this study is to investigate whether Feprazone possesses an antiadipogenic ability in 3 T3-L1 cells and an antiobesity capacity in mouse models. Methods: An MTT assay was used to determine the optimized incubation concentrations of Feprazone in 3 T3-L1 cells. The lipid accumulation was evaluated using Oil Red O staining. The concentrations of triglyceride and glycerol release were detected to check the lipolysis during 3 T3-L1 adipogenesis. A quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expressions of sterol regulatory element-binding protein-1C (SREBP-1C) and fatty acid binding protein 4 (FABP4) in treated cells. The expressions of peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein α (C/EBP-α), adipose triglyceride lipase (ATGL), and aquaporin-7 (AQP-7) were detected using qRT-PCR and Western blot analysis. After the high-fat diet (HFD) mice were treated with Feprazone, the pathological state of adipocyte tissues was evaluated using HE staining. The adipocyte size, visceral adipocyte tissue weight, and bodyweights were recorded. Results: According to the proliferation result, 30 and 60 μM Feprazone were used as the optimized concentrations of Feprazone. In the in vitro study, lipid accumulation, elevated production of triglycerides, the release of glycerol, upregulated SREBP-1C, FABP4, PPAR-γ, and C/EBP-α and downregulated ATGL and AQP-7 in the 3 T3-L1 adipocytes induced by the adipocyte differentiation cocktail medium were significantly reversed by treatment with Feprazone. In the in vivo experiment, we found that the increased adipocyte size, visceral adipocyte tissue weight, and body weights induced by HFD feeding in mice were significantly suppressed by the administration of Feprazone. Conclusion: Feprazone might display anti-adipogenic and antiobesity capacities in in vitro 3 T3-L1 cells and in vivo mice.

Different expression and localization of aquaporin 7 and aquaporin 9 in granulosa cells, oocytes, and embryos of patients with polycystic ovary syndrome and the negatively correlated relationship with insulin regulation

To investigate the expression of aquaporin 7 (AQP7) and aquaporin 9 (AQP9) in the granulosa cells of patients with polycystic ovary syndrome (PCOS) and healthy women and detect their localization in oocytes at the germinal vesicle (GV), metaphase I (MI), MII, embryo, and blastocyst stages and the invitro response to insulin stimulation. Randomized, assessor-blinded study. Reproductive medical center. A total of 40 women (aged 20-38 years) comprising 29 cases of primary infertility and 11 cases of secondary infertility, of whom 17 had an initial diagnosis of PCOS and three received a PCOS diagnosis after an infertility examination. Controlling different concentrations of insulin and different treatment times in cultures of normal human granulosa cells invitro. Expression of AQP7 and AQP9 genes and proteins in granulosa cells detected by real-time quantitative polymerase chain reaction, and localization in oocytes at the GV, MI, MII, embryo, and blastocyst stages by Western blot, immunohistochemical, and immunofluorescence assays, and concentrations of insulin in follicular fluid by enzyme-linked immunosorbent assay. The expression levels of the AQP7 mRNA and protein in the granulosa cells of patients with PCOS were higher than found in healthy controls. We found AQP7 protein expressed in human oocytes at GV, MI, MII, embryo, and blastocyst stages; it was mainly located in the nucleoplasm. In the PCOS group, the expression level of AQP9 mRNA and protein in granulosa cells was lower, and AQP9 protein was expressed in oocytes at the GV, MI, MII, embryo, and blastocyst stages; it was localized on the nuclear membrane. Compared with healthy women, the insulin expression in patients with PCOS was higher. In cultures of normal human granulosa cells invitro, the expression of AQP7 and AQP9 mRNA and protein decreased with the increase in insulin concentration; expression statistically significantly decreased when the insulin concentration was 100 nmol/L, and after 6 to 24 hours of exposure the lowest expression levels were found at 12 hours. The different localization and expression of AQP7 and AQP9 between the two groups suggests that they might be involved in oocyte maturation and embryonic development through different regulatory pathways. The expression levels of AQP7 and AQP9 were negatively correlated with insulin regulation, suggesting that insulin might affect the maturation of PCOS follicles by changing AQP7 and AQP9 expression.