Aquaporin 7 (AQP7), a water/glycerol transporting protein, regulates adipocyte glycerol efflux and influences lipid and glucose homeostasis. Altered AQP7 expression in adults leads to impaired glycerol dynamics, adipocyte hypertrophy and it predisposes them to obesity and diabetes. To assess its possible involvement in childhood obesity, this study investigated the expression of adipocyte AQP7 in cultured adipocytes of children.
Primary in vitro differentiated adipocyte cultures were developed from surgical biopsies of subcutaneous abdominal adipose tissue from 61 (46 prepubertal, 15 pubertal) lean children (body mass index [BMI] <85%) and 41 (22 prepubertal, 19 pubertal) children with obesity (BMI >95%). AQP7 expression was studied by reverse transcription polymerase chain reaction and Western immunoblotting and insulin by enzyme-linked immunosorbent assay.
AQP7 messenger RNA (mRNA) was increased in the younger obese prepubertal (YOP) children but decreased in the obese adolescents (OA) (p=0.014) who also had increased insulin and homeostatic model assessment – insulin resistance (HOMA-IR). Lean pubertal (LP) children and YOP had increased 41 kDa AQP7 protein expression (p=0.001 and p=0.005, respectively). The OA who expressed 34 kDa AQP7 had lower triglyceride (TG) levels than those who did not express it (p=0.013). In the lean children, TG were negatively correlated with 34 kDa AQP7 (p=0.033).
The lower AQP7 mRNA expression in the OA may reflect a predisposition to adipocyte hypertrophy and metabolic dysfunction, as in the adults, whereas the YOP may be protected from this. The increased 41 kDa AQP7 protein expression in the LP may reflect the increased energy requirements of puberty for glycerol while in the YOP it may also be protective against the development of adipocyte hypertrophy.
Disclosure statement: None declared.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: IKY fellowships of excellence for postgraduate studies in Greece – Siemens program. State Scholarships Foundation, Funder Id: 10.13039/ 501100003447, Grant Number: SPhD/11230/13ß.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
1. Tsunoda SP, Wiesner B, Lorenz D, Rosenthal W, Pohl P. Aquaporin-1, nothing but a water channel. J Biol Chem 2004;279:11364–7. Search in Google Scholar
2. Madeira A, Camps M, Zorzano A, Moura TF, Soveral G. Biophysical assessment of human aquaporin-7 as a water and glycerol channel in 3T3-L1 adipocytes. PLoS One 2013;8:e83442. Search in Google Scholar
3. Reshef L, Olswang Y, Cassuto H, Blum B, Croniger CM, et al. Glyceroneogenesis and the triglyceride/fatty acid cycle. J Biol Chem 2003;278:30413–6. Search in Google Scholar
4. Marrades MP, Milagro FI, Martinez JA, Moreno-Aliaga MJ. Differential expression of aquaporin 7 in adipose tissue of lean and obese high fat consumers. Biochem Biophys Res Commun 2006;339:785–9. Search in Google Scholar
5. Miranda M, Escote X, Ceperuelo-Mallafre V, Alcaide MJ, Simon I, et al. Paired subcutaneous and visceral adipose tissue aquaporin-7 expression in human obesity and type 2 diabetes: differences and similarities between depots. J Clin Endocrinol Metab 2010;95:3470–9. Search in Google Scholar
6. Hibuse T, Maeda N, Funahashi T, Yamamoto K, Nagasawa A, et al. Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase. Proc Natl Acad Sci USA 2005;102:10993–8. Search in Google Scholar
7. Kuriyama H, Shimomura I, Kishida K, Kondo H, Furuyama N, et al. Coordinated regulation of fat-specific and liver-specific glycerol channels, aquaporin adipose and aquaporin 9. Diabetes 2002;51:2915–21. Search in Google Scholar
8. Rodriguez A, Catalan V, Gomez-Ambrosi J, Fruhbeck G. Aquaglyceroporins serve as metabolic gateways in adiposity and insulin resistance control. Cell Cycle 2011;10:1548–56. Search in Google Scholar
9. Kishida K, Kuriyama H, Funahashi T, Shimomura I, Kihara S, et al. Aquaporin adipose, a putative glycerol channel in adipocytes. J Biol Chem 2000;275:20896–902. Search in Google Scholar
10. Rodriguez A, Catalan V, Gomez-Ambrosi J, Garcia-Navarro S, Rotellar F, et al. Insulin- and leptin-mediated control of aquaglyceroporins in human adipocytes and hepatocytes is mediated via the PI3K/Akt/mTOR signaling cascade. J Clin Endocrinol Metab 2011;96:E586–97. Search in Google Scholar
11. Kishida K, Shimomura I, Kondo H, Kuriyama H, Makino Y, et al. Genomic structure and insulin-mediated repression of the aquaporin adipose (AQPap), adipose-specific glycerol channel. J Biol Chem 2001;276:36251–60. Search in Google Scholar
12. Lebeck J, Ostergard T, Rojek A, Fuchtbauer EM, Lund S, et al. Gender-specific effect of physical training on AQP7 protein expression in human adipose tissue. Acta Diabetol 2012;49(Suppl 1):S215–26. Search in Google Scholar
13. Wakayama Y, Hirako S, Ogawa T, Jimi T, Shioda S. Upregulated expression of AQP 7 in the skeletal muscles of obese ob/ob mice. Acta Histochem Cytochem 2014;47:27–33. Search in Google Scholar
14. Hibuse T, Maeda N, Nakatsuji H, Tochino Y, Fujita K, et al. The heart requires glycerol as an energy substrate through aquaporin 7, a glycerol facilitator. Cardiovasc Res 2009;83: 34–41. Search in Google Scholar
15. Nejsum LN, Elkjaer M, Hager H, Frokiaer J, Kwon TH, et al. Localization of aquaporin-7 in rat and mouse kidney using RT-PCR, immunoblotting, and immunocytochemistry. Biochem Biophys Res Commun 2000;277:164–70. Search in Google Scholar
16. Saito K, Kageyama Y, Okada Y, Kawakami S, Kihara K, et al. Localization of aquaporin-7 in human testis and ejaculated sperm: possible involvement in maintenance of sperm quality. J Urol 2004;172(5 Pt 1):2073–6. Search in Google Scholar
17. Laforenza U, Gastaldi G, Grazioli M, Cova E, Tritto S, et al. Expression and immunolocalization of aquaporin-7 in rat gastrointestinal tract. Biol Cell 2005;97:605–13. Search in Google Scholar
18. Louchami K, Best L, Brown P, Virreira M, Hupkens E, et al. A new role for aquaporin 7 in insulin secretion. Cell Physiol Biochem 2012;29:65–74. Search in Google Scholar
19. Kuriyama H, Kawamoto S, Ishida N, Ohno I, Mita S, et al. Molecular cloning and expression of a novel human aquaporin from adipose tissue with glycerol permeability. Biochem Biophys Res Commun 1997;241:53–8. Search in Google Scholar
20. Prieto-Martinez N, Vilagran I, Morato R, Rodriguez-Gil JE, Yeste M, et al. Aquaporins 7 and 11 in boar spermatozoa: detection, localisation and relationship with sperm quality. Reprod Fertil Dev 2016;28:663–72. Search in Google Scholar
21. Bremer AA, Jialal I. Adipose tissue dysfunction in nascent metabolic syndrome. J Obes 2013;2013:393192. Search in Google Scholar
22. Whitlock EP, Williams SB, Gold R, Smith PR, Shipman SA. Screening and interventions for childhood overweight: a summary of evidence for the US Preventive Services Task Force. Pediatrics 2005;116:e125–44. Search in Google Scholar
23. Freedman DS, Mei Z, Srinivasan SR, Berenson GS, Dietz WH. Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa Heart Study. J Pediatr 2007;150:12–7.e2. Search in Google Scholar
24. Schonbeck Y, Talma H, van Dommelen P, Bakker B, Buitendijk SE, et al. Increase in prevalence of overweight in Dutch children and adolescents: a comparison of nationwide growth studies in 1980, 1997 and 2009. PLoS One 2011;6:e27608. Search in Google Scholar
25. McCarthy HD, Jarrett KV, Crawley HF. The development of waist circumference percentiles in British children aged 5.0–16.9 y. Eur J Clin Nutr 2001;55:902–7. Search in Google Scholar
26. Karvela A, Rojas-Gil AP, Samkinidou E, Papadaki H, Pappa A, et al. Endocannabinoid (EC) receptor, CB1, and EC enzymes’ expression in primary adipocyte cultures of lean and obese pre-pubertal children in relation to adiponectin and insulin. J Pediatr Endocrinol Metab 2010;23:1011–24. Search in Google Scholar
27. Lann D, LeRoith D. Insulin resistance as the underlying cause for the metabolic syndrome. Med Clin North Am 2007;91:1063–77, viii. Search in Google Scholar
28. Rodriguez LT, Friedman KA, Coffman SS, Heller A. Effect of the sensor site-insulin injection site distance on the dynamics of local glycemia in the minipig model. Diabetes Technol Ther 2011;13:489–93. Search in Google Scholar
29. Dicker A, Astrom G, Sjolin E, Hauner H, Arner P, et al. The influence of preadipocyte differentiation capacity on lipolysis in human mature adipocytes. Horm Metab Res 2007;39:282–7. Search in Google Scholar
30. Famulla S, Schlich R, Sell H, Eckel J. Differentiation of human adipocytes at physiological oxygen levels results in increased adiponectin secretion and isoproterenol-stimulated lipolysis. Adipocyte 2012;1:132–81. Search in Google Scholar
31. Hannon TS, Janosky J, Arslanian SA. Longitudinal study of physiologic insulin resistance and metabolic changes of puberty. Pediatr Res 2006;60:759–63. Search in Google Scholar
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