Skip to main content Accessibility help
×
Home

Modulation of aquaporin gene expression by n-3 long-chain PUFA lipid structures in white and brown adipose tissue from hamsters

  • Paula A. Lopes (a1), Rute Martins (a2) (a3), Inês Vieira da Silva (a2) (a3), Marta S. Madeira (a1), José A. M. Prates (a1) and Graça Soveral (a2) (a3)...

Abstract

EPA (20 : 5n-3) and DHA (22 : 6n-3) fatty acids have weight-reducing properties with physiological activity depending on their molecular structure – that is, as TAG or ethyl esters (EE). Aquaporins (AQP) are membrane protein channels recognised as important players in fat metabolism, but their differential expression in white adipose tissue (WAT) and brown adipose tissue (BAT), as well as their modulation by dietary n-3 long-chain PUFA (LCPUFA) such as EPA and DHA, has never been investigated. In this study, the transcriptional profiles of AQP3, AQP5, AQP7 and selected lipid markers of WAT (subcutaneous and visceral) and BAT (interscapular) from hamsters fed diets containing n-3 LCPUFA in different lipid structures such as fish oil (FO, rich in EPA and DHA in the TAG form) and FO-EE (rich in EPA and DHA in the EE form) were used and compared with linseed oil (LSO) as the reference group. A clear effect of fat depot was observed for AQP3 and leptin (LEP), with the lowest values of mRNA found in BAT relative to WAT. The opposite occurred for PPARα. AQP7 was affected by diet, with FO-fed hamsters having higher mRNA levels compared with LSO-fed hamsters. The relative gene expression of AQP5, adiponectin (ADIPO), GLUT4 and PPARγ was influenced by both fat tissue and diet. Taken together, our results revealed a differential expression profile of AQP and some markers of lipid metabolism in both WAT and BAT in response to feeding n-3 LCPUFA in two different structural formats: TAG v. EE.

Copyright

Corresponding author

*Corresponding authors: P. A. Lopes, fax +351 213652829, email ampalopes@fmv.ulisboa.pt; G. Soveral, fax +351 217946470, email gsoveral@ff.ulisboa.pt

Footnotes

Hide All

These authors contributed equally to this work.

Footnotes

References

Hide All
1. Simopoulos, AP (2008) The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease. Asia Pac J Clin Nutr 17, 131134.
2. Ravussin, E & Kozak, LP (2009) Have we entered the brown adipose tissue renaissance? Obes Rev 10, 265268.
3. Calder, P (2006) n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83, 1505S1519S.
4. Rodrigues, PO, Martins, SV, Lopes, PA, et al. (2014) Influence of feeding graded levels of canned sardines on the inflammatory markers and tissue fatty acid composition of Wistar rats. Br J Nutr 112, 309319.
5. Todorčević, M & Hodson, L (2016) The effect of marine derived n-3 fatty acids on adipose tissue metabolism and function. J Clin Med 5, 327.
6. Bandarra, NM, Lopes, PA, Martins, SV, et al. (2016) Docosahexaenoic acid at the sn-2 position of structured triacylglycerols improved n-3 polyunsaturated fatty acid assimilation in tissues of hamsters. Nutr Res 36, 452463.
7. Lee, YH, Mottillo, EP & Granneman, JG (2014) Adipose tissue plasticity from WAT to BAT and in between. Biochim Biophys Acta 1842, 358369.
8. Park, HT, Lee, ES, Cheon, YP, et al. (2012) The relationship between fat depot-specific preadipocyte differentiation and metabolic syndrome in obese women. Clin Endocrinol 76, 5966.
9. Barbatelli, G, Murano, I, Madsen, L, et al. (2010) The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab 298, E1244E1253.
10. Capurso, C & Capurso, A (2012) From excess adiposity to insulin resistance: the role of free fatty acids. Vascul Pharmacol 57, 9197.
11. Fruhbeck, G, Mendez-Gimenez, L, Fernandez-Formoso, JA, et al. (2014) Regulation of adipocyte lipolysis. Nutr Res Rev 27, 6393.
12. Birerdinc, A, Jarrar, M, Stotish, T, et al. (2013) Manipulating molecular switches in brown adipocytes and their precursors: a therapeutic potential. Prog Lipid Res 52, 5161.
13. Virtanen, KA & Nuutila, P (2011) Brown adipose tissue in humans. Curr Opin Lipidol 22, 4954.
14. Virtanen, KA, Lidell, ME, Orava, J, et al. (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360, 15181525.
15. van Marken Lichtenbelt, WD, Vanhommerig, JW, Smulders, NM, et al. (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360, 15001508.
16. Smorlesi, A, Frontini, A, Giordano, S, et al. (2012) The adipose organ: white-brown adipocyte plasticity and metabolic inflammation. Obes Rev 13, Suppl. 2, 8396.
17. Agre, P (2004) Aquaporin water channels (Nobel Lecture). Angew Chem Int Ed Engl 43, 42784290.
18. Verkman, AS (2005) More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci 118, 32253232.
19. Rojek, A, Praetorius, J, Frøkiaer, J, et al. (2008) A current view of the mammalian aquaglyceroporins. Annu Rev Physiol 70, 301327.
20. Ishibashi, K, Tanaka, Y & Morishita, Y (2014) The role of mammalian superaquaporins inside the cell. Biochim Biophys Acta 1840, 15071512.
21. Madeira, A, Fernández-Veledo, S, Camps, M, et al. (2014) Human aquaporin-11 is a water and glycerol channel and localizes in the vicinity of lipid droplets in human adipocytes. Obesity (Silver Spring) 22, 20102017.
22. Fruhbeck, G (2005) Obesity: aquaporin enters the picture. Nature 438, 436438.
23. Rodríguez, A, Catalan, V, Gomez-Ambrosi, J, et al. (2011) Aquaglyceroporins serve as metabolic gateways in adiposity and insulin resistance control. Cell Cycle 10, 15481556.
24. da Silva, IV, Rodrigues, JS, Rebelo, I, et al. (2018) Revisiting the metabolic syndrome: the emerging role of aquaglyceroporins. Cell Mol Life Sci 75, 19731988.
25. Kishida, K, Kuriyama, H, Funahashi, T, et al. (2000) Aquaporin adipose, a putative glycerol channel in adipocytes. J Biol Chem 275, 2089620902.
26. Kondo, H, Shimomura, I, Kishida, K, et al. (2002) Human aquaporin adipose (AQPap) gene. Genomic structure, promoter analysis and functional mutation. Eur J Biochem 269, 18141826.
27. Hibuse, T, Maeda, N, Funahashi, T, et al. (2005) Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase. Proc Natl Acad Sci U S A 102, 1099310998.
28. Madeira, A, Camps, M, Zorzano, A, et al. (2013) Biophysical assessment of human aquaporin-7 as a water and glycerol channel in 3T3-L1 adipocytes. PLOS ONE 8, e83442.
29. Laforenza, U, Scaffino, MF & Gastaldi, G (2013) Aquaporin-10 represents an alternative pathway for glycerol efflux from human adipocytes. PLOS ONE 8, e54474.
30. Rodriguez, A, Catalan, V, Gomez-Ambrosi, J, et al. (2011) 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 96, E586E597.
31. Miranda, M, Escote, X, Ceperuelo-Mallafre, V, et al. (2010) 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 95, 34703479.
32. Madeira, A, Mósca, AF, Moura, TF, et al. (2015) Aquaporin-5 is expressed in adipocytes with implications in adipose differentiation. IUBMB Life 67, 5460.
33. Yin, W, Carballo-Jane, E, McLaren, DG, et al. (2012) Plasma lipid profiling across species for the identification of optimal animal models of human dyslipidemia. J Lipid Res 53, 5165.
34. Dalboge, LS, Pedersen, PJ, Hansen, G, et al. (2015) A hamster model of diet-induced obesity for preclinical evaluation of anti-obesity, anti-diabetic and lipid modulating agents. PLOS ONE 10, 634648.
35. Lopes, PA, Bandarra, NM, Martins, SV, et al. (2017) Docosahexaenoic acid (DHA) at the sn-2 position of triacylglycerols increases DHA incorporation in brown, but not in white adipose tissue, of hamsters. Int J Food Sci Nutr 69, 458471.
36. Itah, R, Gitelman, I & Davis, C (2004) A replacement for methoxyflurane (Metofane) in open-circuit anaesthesia. Lab Anim 38, 280285.
37. Livak, KJ & Schmittgen, TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25, 402408.
38. Fleige, S & Pfaffl, MW (2006) RNA integrity and the effect on the real-time qRT-PCR performance. Mol Aspects Med 27, 126139.
39. Baylin, A, Kabagambe, EK, Siles, X, et al. (2002) Adipose tissue biomarkers of fatty acid intake. Am J Clin Nutr 76, 750757.
40. Madeira, A, Moura, TF & Soveral, G (2015) Aquaglyceroporins: implications in adipose biology and obesity. Cell Mol Life Sci 72, 759771.
41. da Silva, IV & Soveral, G (2017) Aquaporins in obesity. Adv Exp Med Biol 969, 227238.
42. Fruhbeck, G, Catalan, V, Gomez-Ambrosi, J, et al. (2006) Aquaporin-7 and glycerol permeability as novel obesity drug-target pathways. Trends Pharmacol Sci 27, 345347.
43. Cao, H (2014) Adipocytokines in obesity and metabolic disease. J Endocrinol 220, 4759.
44. Bastard, JP, Maachi, M, Lagathu, C, et al. (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17, 412.
45. Cowherd, RM, Lyle, RE & McGehee, RE Jr (1999) Molecular regulation of adipocyte differentiation. Semin Cell Dev Biol 10, 310.
46. Rodríguez, A, Moreno, NR, Balaguer, I, et al. (2015) Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice. Sci Rep 5, 12067.
47. Wang, GX, Zhao, XY & Lin, JD (2015) The brown fat secretome: metabolic functions beyond thermogenesis. Trends Endocrinol Metab 26, 231237.
48. Zhang, Y, Matheny, M, Zolotukhin, S, et al. (2002) Regulation of adiponectin and leptin gene expression in white and brown adipose tissues: influence of beta3-adrenergic agonists, retinoic acid, leptin and fasting. Biochim Biophys Acta 1584, 115122.
49. Iacobellis, G, Di Gioia, C, Petramala, L, et al. (2013) Brown fat expresses adiponectin in humans. Int J Endocrinol 2013, 126751.
50 Kersten, S, Desvergne, B & Wahli, W (2000) Roles of PPARs in health and disease. Nature 405, 421424.
51. Guan, HP, Li, Y, Jensen, MV, et al. (2002) A futile metabolic cycle activated in adipocytes by antidiabetic agents. Nat Med 8, 11221128.
52. Tordjman, J, Khazen, W, Antoine, B, et al. (2003) Regulation of glyceroneogenesis and phosphoenolpyruvate carboxykinase by fatty acids, retinoic acids and thiazolidinediones: potential relevance to type 2 diabetes. Biochimie 85, 12131218.
53. Kishida, K, Shimomura, I & Nishizawa, H (2001) Enhancement of the aquaporin adipose gene expression by a peroxisome proliferator-activated receptor gamma. J Biol Chem 276, 4857248579.
54. Peirce, V, Carobbio, S & Vidal-Puig, A (2014) The different shades of fat. Nature 510, 7683.
55. Lawson, LD & Hughes, BG (1988) Absorption of eicosapentaenoic acid and docosahexaenoic acid from fish oil triacylglycerols or fish oil ethyl esters co-ingested with a high-fat meal. Biochem Biophys Res Comm 156, 960963.
56. Lawson, LD & Hughes, BG (1988) Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters. Biochem Biophys Res Comm 152, 328335.
57. Beckermann, B, Beneke, M & Seitz, I (1990) Comparative bioavailability of eicosapentaenoic acid and docosahexaenoic acid from triglycerides, free fatty acids and ethyl esters in volunteers. Arzneimittelforschung 40, 700704.
58. Song, JH, Inoue, Y & Miyazawa, T (1997) Oxidative stability of docosahexaenoic acid containing oils in the form of phospholipids, triacylglycerols, and ethyl esters. Biosci Biotechnol Biochem 61, 20852088.
59. Yoshii, H, Furuta, T, Siga, H, et al. (2002) Autoxidation kinetic analysis of docosahexaenoic acid ethyl ester and docosahexaenoic triglyceride with oxygen sensor. Biosci Biotechnol Biochem 66, 749753.

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed