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Influence of Morbid Obesity and Insulin Resistance on Gene Expression Levels of AQP7 in Visceral Adipose Tissue and AQP9 in Liver

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Abstract

Background

Glycerol production and its efflux from adipocytes to the liver are key to modulate lipid and glucose homeostasis. Aquaporin 7 (AQP7) is an aquaglyceroporin that acts as the adipose glycerol channel, whereas aquaporin 9 (AQP9) is the specific channel operating in the liver. The aim of the present work was to evaluate the effect of obesity and type 2 diabetes mellitus (T2DM) on gene expression levels of AQP7 in visceral adipose tissue (VAT) and AQP9 in liver.

Methods

VAT and liver biopsies obtained from 20 women were used in the study. Patients were classified as lean or obese with the last group being further subclassified as normoglycemic (NG), patients with impaired glucose tolerance (IGT), or with T2DM. Anthropometric measurements as well as circulating metabolites, hormones, and adipokines were determined. Real-time polymerase chain reaction analyses were performed to quantify transcript levels of AQP7 in VAT and AQP9 in the liver.

Results

Gene expression levels of AQP7 in VAT showed a tendency toward an increase (P = 0.065) in obese patients (both NG and T2DM) compared to lean subjects. AQP9 showed a significant downregulation in the hepatic biopsies obtained from obese T2DM patients compared to obese NG and IGT patients (P = 0.028).

Conclusion

The tendency toward an elevation of mRNA expression of VAT AQP7 in obesity together with the decreased hepatic AQP9 expression observed in obese T2DM subjects suggests a potential role in facilitating glycerol release from adipose tissue and reducing glycerol entry into hepatocytes in obesity and T2DM, respectively.

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Abbreviations

BF:

body fat percentage

BMI:

body mass index

AQP7:

aquaporin 7

AQP9:

aquaporin 9

NG:

normoglycemic

OGTT:

oral glucose tolerance test

T2DM:

type 2 diabetes mellitus

VAT:

visceral adipose tissue

References

  1. Frühbeck G, Gómez-Ambrosi J, Muruzábal FJ, et al. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab. 2001;280:E827–47.

    PubMed  Google Scholar 

  2. Frühbeck G, Gómez-Ambrosi J. Control of body weight: a physiologic and transgenic perspective. Diabetologia. 2003;46:143–72.

    PubMed  Google Scholar 

  3. Duncan RE, Ahmadian M, Jaworski K, et al. Regulation of lipolysis in adipocytes. Annu Rev Nutr. 2007;27:79–101.

    Article  PubMed  CAS  Google Scholar 

  4. Landau BR, Wahren J, Previs SF, et al. Glycerol production and utilization in humans: sites and quantitation. Am J Physiol. 1996;271:E1110–7.

    PubMed  CAS  Google Scholar 

  5. Reshef L, Olswang Y, Cassuto H, et al. Glyceroneogenesis and the triglyceride/fatty acid cycle. J Biol Chem. 2003;278:30413–6.

    Article  PubMed  CAS  Google Scholar 

  6. Kuriyama H, Shimomura I, Kishida K, et al. Coordinated regulation of fat-specific and liver-specific glycerol channels, aquaporin adipose and aquaporin 9. Diabetes. 2002;51:2915–21.

    Article  PubMed  CAS  Google Scholar 

  7. Denker BM, Smith BL, Kuhajda FP, et al. Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules. J Biol Chem. 1988;263:15634–42.

    PubMed  CAS  Google Scholar 

  8. King LS, Kozono D, Agre P. From structure to disease: the evolving tale of aquaporin biology. Nat Rev Mol Cell Biol. 2004;5:687–98.

    Article  PubMed  CAS  Google Scholar 

  9. Rodríguez A, Catalán V, Gómez-Ambrosi J, et al. Role of aquaporin-7 in the pathophysiological control of fat accumulation in mice. FEBS Lett. 2006;580:4771–6.

    Article  PubMed  CAS  Google Scholar 

  10. Kuriyama H, Kawamoto S, Ishida N, 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.

    Article  PubMed  CAS  Google Scholar 

  11. Frühbeck G, Catalán V, Gómez-Ambrosi J, et al. Aquaporin-7 and glycerol permeability as novel obesity drug-target pathways. Trends Pharmacol Sci. 2006;27:345–7.

    Article  PubMed  CAS  Google Scholar 

  12. Hibuse T, Maeda N, Nagasawa A, et al. Aquaporins and glycerol metabolism. Biochim Biophys Acta. 2006;1758:1004–11.

    Article  PubMed  CAS  Google Scholar 

  13. Frühbeck G. Obesity: aquaporin enters the picture. Nature. 2005;438:436–7.

    Article  PubMed  CAS  Google Scholar 

  14. Kishida K, Kuriyama H, Funahashi T, et al. Aquaporin adipose, a putative glycerol channel in adipocytes. J Biol Chem. 2000;275:20896–902.

    Article  PubMed  CAS  Google Scholar 

  15. Sjöholm K, Palming J, Olofsson LE, et al. A microarray search for genes predominantly expressed in human omental adipocytes: adipose tissue as a major production site of serum amyloid A. J Clin Endocrinol Metab. 2005;90:2233–9.

    Article  PubMed  CAS  Google Scholar 

  16. Maeda N, Funahashi T, Hibuse T, et al. Adaptation to fasting by glycerol transport through aquaporin 7 in adipose tissue. Proc Natl Acad Sci USA. 2004;101:17801–6.

    Article  PubMed  CAS  Google Scholar 

  17. Hara-Chikuma M, Sohara E, Rai T, et al. Progressive adipocyte hypertrophy in aquaporin-7-deficient mice: adipocyte glycerol permeability as a novel regulator of fat accumulation. J Biol Chem. 2005;280:15493–6.

    Article  PubMed  CAS  Google Scholar 

  18. Hibuse T, Maeda N, Funahashi T, 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.

    Article  PubMed  CAS  Google Scholar 

  19. Elkjaer M, Vajda Z, Nejsum LN, et al. Immunolocalization of AQP9 in liver, epididymis, testis, spleen, and brain. Biochem Biophys Res Commun. 2000;276:1118–28.

    Article  PubMed  CAS  Google Scholar 

  20. Rojek AM, Skowronski MT, Fuchtbauer EM, et al. Defective glycerol metabolism in aquaporin 9 (AQP9) knockout mice. Proc Natl Acad Sci USA. 2007;104:3609–14.

    Article  PubMed  CAS  Google Scholar 

  21. Carbrey JM, Gorelick-Feldman DA, Kozono D, Praetorius J, Nielsen S, Agre P. Aquaglyceroporin AQP9: solute permeation and metabolic control of expression in liver. Proc Natl Acad Sci USA. 2003;100:2945–50.

    Article  PubMed  CAS  Google Scholar 

  22. Marrades MP, Milagro FI, Martínez JA, et al. Differential expression of aquaporin 7 in adipose tissue of lean and obese high fat consumers. Biochem Biophys Res Commun. 2006;339:785–9.

    Article  PubMed  CAS  Google Scholar 

  23. Prudente S, Flex E, Morini E, et al. A functional variant of the adipocyte glycerol channel aquaporin 7 gene is associated with obesity and related metabolic abnormalities. Diabetes. 2007;56:1468–74.

    Article  PubMed  CAS  Google Scholar 

  24. Ceperuelo-Mallafré V, Miranda M, Chacón MR, et al. Adipose tissue expression of the glycerol channel aquaporin-7 gene is altered in severe obesity but not in type 2 diabetes. J Clin Endocrinol Metab. 2007;92:3640–5.

    Article  PubMed  CAS  Google Scholar 

  25. Das SK, Roberts SB, Kehayias JJ, et al. Body composition assessment in extreme obesity and after massive weight loss induced by gastric bypass surgery. Am J Physiol Endocrinol Metab. 2003;284:E1080–8.

    PubMed  CAS  Google Scholar 

  26. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  PubMed  CAS  Google Scholar 

  27. Katz A, Nambi SS, Mather K, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85:2402–10.

    Article  PubMed  CAS  Google Scholar 

  28. Gómez-Ambrosi J, Salvador J, Rotellar F, et al. Increased serum amyloid A concentrations in morbid obesity decrease after gastric bypass. Obes Surg. 2006;16:262–9.

    Article  PubMed  Google Scholar 

  29. Catalán V, Gómez-Ambrosi J, Ramírez B, et al. Proinflammatory cytokines in obesity: impact of type 2 diabetes mellitus and gastric bypass. Obes Surg. 2007;17:1464–74.

    Article  PubMed  Google Scholar 

  30. Gómez-Ambrosi J, Catalán V, Diez-Caballero A, et al. Gene expression profile of omental adipose tissue in human obesity. FASEB J. 2004;18:215–7.

    PubMed  Google Scholar 

  31. Catalán V, Gómez-Ambrosi J, Rotellar F, et al. Validation of endogenous control genes in human adipose tissue: relevance to obesity and obesity-associated type 2 diabetes mellitus. Horm Metab Res. 2007;39:495–500.

    Article  PubMed  CAS  Google Scholar 

  32. Catalán V, Gómez-Ambrosi J, Rotellar F, et al. The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus. Clin Endocrinol. 2007;66:598–601.

    Google Scholar 

  33. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21:697–738.

    Article  PubMed  CAS  Google Scholar 

  34. Rodríguez A, Catalán V, Gómez-Ambrosi J, et al. Visceral and subcutaneous adiposity: are both potential therapeutic targets for tackling the metabolic syndrome? Curr Pharm Des. 2007;21:2169–75.

    Article  Google Scholar 

  35. Kishida K, Shimomura I, Nishizawa H, et al. Enhancement of the aquaporin adipose gene expression by a peroxisome proliferator activated receptor γ. J Biol Chem. 2001;276:48572–9.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by FIS PI030381, PI061458, and PI06/90288 from the Spanish Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo and by the Department of Health of the Gobierno de Navarra (48/2003 and 20/2005) of Spain. The authors gratefully acknowledge the valuable collaboration of the surgery assistant nurses and the members of the Multidisciplinary Obesity Team. CIBER de Fisiopatología de la Obesidad y Nutrción (CIBEROBN) is an initiative of the Instituto de Salud Carlos III, Spain.

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Correspondence to Gema Frühbeck.

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Catalán, V., Gómez-Ambrosi, J., Pastor, C. et al. Influence of Morbid Obesity and Insulin Resistance on Gene Expression Levels of AQP7 in Visceral Adipose Tissue and AQP9 in Liver. OBES SURG 18, 695–701 (2008). https://doi.org/10.1007/s11695-008-9453-7

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  • DOI: https://doi.org/10.1007/s11695-008-9453-7

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