Glycerol Metabolism Alteration in Adipocytes from n3-PUFA-Depleted Rats, an Animal Model for Metabolic Syndrome

Abstract

Aquaglyceroporin 7 (AQP7) is a glycerol transporter expressed in adipocytes. Its expression has been shown to be modulated in obesity. Metabolic syndrome is characterized by abdominal obesity, insulin resistance, dyslipidemia, and hypertension. An animal model displaying several features of metabolic syndrome was used to study the AQP7 expression at both mRNA and protein level and glycerol flux in adipocytes. Second generation n3-PUFA depleted female rats is a good animal model for metabolic syndrome as it displays characteristic features such as liver steatosis, visceral obesity, and insulin resistance. Our data show a reduced expression of AQP7 at the protein level in adipose tissue from n3-PUFA-depleted rats, without any changes at the mRNA levels. [U-¹⁴C]-Glycerol uptake was not modified in adipocytes from n3-PUFA-depleted animals.

Key words

aquaporins - fat cell - lipid metabolism

• References

• 1 Agre P. Aquaporin water channels (Nobel Lecture). Angew Chem Int Ed 2004; 43: 4278-4290
• 2 Verkman AS. Novel roles of aquaporins revealed by phenotype analysis of knockout mice. Rev Physiol Biochem Pharmacol 2005; 155: 31-55
• 3 Smith BL, Agre P. Erythrocyte Mr-28,000 Transmembrane Protein Exists As A Multisubunit Oligomer Similar to Channel Proteins. J Biol Chem 1991; 266: 6407-6415
• 4 Preston GM, Agre P. Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: member of an ancient channel family. Proc Natl Acad Sci USA 1991; 88: 11110-11114
• 5 Krane CM, Goldstein DL. Comparative functional analysis of aquaporins/glyceroporins in mammals and anurans. Mamm Genome 2007; 18: 452-462
• 6 Rojek A, Praetorius J, Frokiaer J, Nielsen S, Fenton RA. A current view of the mammalian aquaglyceroporins. Annu Rev Physiol 2008; 70: 301-327
• 7 Ishibashi K. Aquaporin subfamily with unusual NPA boxes. Biochim Biophys Acta 2006; 1758: 989-993
• 8 Ishibashi K, Kuwahara M, Gu Y, Kageyama T, Tohsaka A, Susuki F, Marumo F, Sasaki S. Cloning and functional expression of a new water channel abundantly expressed in the testis permeable to water, glycerol, and urea. J Biol Chem 1997; 272: 20782-20786
• 9 Kishida K, Shimomura I, Kondo H, Kuriyama H, Makino Y, Nishizawa H, Maeda N, Matsuda M, Ouchi N, Kihara S, Kurachi Y, Funahashi T, Matsuzawa Y. Genomic structure and insulin-mediated repression of the aquaporin adipose (AQPap), adipose-specific glycerol channel. J Biol Chem 2001; 276: 36251-36260
• 10 Hara-Chikuma M, Sohara E, Rai T, Ikawa M, Okabe M, Sasaki S, Uchida S, Verkman AS. Progressive adipocyte hypertrophy in aquaporin-7-deficient mice: adipocyte glycerol permeability as a novel regulator of fat accumulation. J Biol Chem 2005; 280: 15493-15496
• 11 Jiamsripong P, Mookadam M, Honda T, Khandheria BK, Mookadam F. The metabolic syndrome and cardiovascular disease: part I. Prev Cardiol 2008; 11: 155-161
• 12 Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith Jr SC. Harmonizing the Metabolic Syndrome: A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120: 1640-1645
• 13 Daram SR, Boppidi H. Nonalcoholic Fatty Liver Disease: Hepatic Manifestation of Obesity and the Metabolic Syndrome. Postgrad Med 2008; 120: E01-E07
• 14 Roche HM, Phillips C, Gibney MJ. The metabolic syndrome: the crossroads of diet and genetics. Proc Nutr Soc 2005; 64: 371-377
• 15 Carpentier YA, Portois L, Malaisse WJ. n-3 Fatty acids and the metabolic syndrome. Am J Clin Nutr 2006; 83: S1499-S1504
• 16 Barre DE. The role of consumption of alpha-linolenic, eicosapentaenoic and docosahexaenoic acids in human metabolic syndrome and type 2 diabetes – a mini-review. J Oleo Sci 2007; 56: 319-325
• 17 Lombardo YB, Hein G, Chicco A. Metabolic syndrome: effects of n-3 PUFAs on a model of dyslipidemia, insulin resistance and adiposity. Lipids 2007; 42: 427-437
• 18 Benatti P, Peluso G, Nicolai R, Calvani M. Polyunsaturated Fatty Acids: Biochemical, Nutritional and Epigenetic Properties. J Am Coll Nutr 2004; 23: 281-302
• 19 Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 2002; 56: 365-379
• 20 Cancelas J, Prieto PG, Villanueva-Penacarrillo ML, Zhang Y, Portois L, Sener A, Carpentier YA, Valverde I, Malaisse WJ. Glucose intolerance associated to insulin resistance and increased insulin secretion in rats depleted in long-chain omega3 fatty acids. Horm Metab Res 2007; 39: 823-825
• 21 Armitage JA, Pearce AD, Sinclair AJ, Vingrys AJ, Weisinger RS, Weisinger HS. Increased blood pressure later in life may be associated with perinatal n-3 fatty acid deficiency. Lipids 2003; 38: 459-464
• 22 Peltier S, Malaisse WJ, Portois L, Demaison L, Novel-Chate V, Chardigny JM, Sebedio JL, Carpentier YA, Leverve XM. Acute in vivo administration of a fish oil-containing emulsion improves post-ischemic cardiac function in n-3-depleted rats. Int J Mol Med 2006; 18: 741-749
• 23 Oguzhan B, Sancho V, Acitores A, Villanueva-Penacarrillo ML, Portois L, Chardigny JM, Sener A, Carpentier YA, Malaisse WJ. Alteration of adipocyte metabolism in omega3 fatty acid-depleted rats. Horm Metab Res 2006; 38: 789-798
• 24 Oguzhan B, Zhang Y, Louchami K, Courtois P, Portois L, Chardigny JM, Malaisse WJ, Carpentier YA, Sener A. Pancreatic islet function in omega3 fatty acid-depleted rats: Glucose metabolism and nutrient-stimulated insulin release. Endocrine 2006; 29: 457-466
• 25 Childs CE, Romeu-Nadal M, Burdge G, Calder P. The polyunsaturated fatty acid composition of hepatic and plasma lipids differ by both sex and dietary fat intake in rats. J Nutr 2009; 140: 245-250
• 26 Simoens CH, Richelle M, Rössle C, Derluyn M, Deckelbaum RJ, Carpentier YA. Manipulation of tissue fatty acid profile by intravenous lipids in dogs. Clin Nutr 1995; 14: 177-185
• 27 Wong ML, Medrano JF. Real-time PCR for mRNA quantitation. Biotechniques 2005; 39: 75-85
• 28 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-[delta][delta]CT method. Methods 2001; 25: 402-408
• 29 Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002; 3 research0034–research0034.11
• 30 Rodbell M. Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 1964; 2339: 375-380
• 31 Sancho V, Trigo MV, Gonzalez N, Valverde I, Malaisse W, Villanueva-Penacarrillo ML. Effects of glucagon-like peptide-1 and exendins on kinase activity, glucose transport and lipid metabolism in adipocytes from normal and type-2 diabetic rats. J Mol Endocrinol 2005; 35: 27-38
• 32 Kuriyama H, Shimomura I, Kishida K, Kondo H, Furuyama N, Nishizawa H, Maeda N, Matsuda M, Nagaretani H, Kihara S, Nakamura T, Tochino Y, Funahashi T, Matsuzawa Y. Coordinated regulation of fat-specific and liver-specific glycerol channels, aquaporin adipose and aquaporin 9. Diabetes 2002; 51: 2915-2921
• 33 Hibuse T, Maeda N, Funahashi T, Yamamoto K, Nagasawa A, Mizunoya W, Kishida K, Inoue K, Kuriyama H, Nakamura T, Fushiki T, Kihara S, Shimomura I. Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase. Proc Natl Acad Sci USA 2005; 102: 10993-10998
• 34 Matsumura K, Chang BHJ, Fujimiya M, Chen W, Kulkarni RN, Eguchi Y, Kimura H, Kojima H, Chan L. Aquaporin 7 is a beta-cell protein and regulator of intraislet glycerol content and glycerol kinase activity, beta-cell mass, and insulin production and secretion. Mol Cell Biol 2007; 27: 6026-6037
• 35 Foss EJ, Radulovic D, Shaffer SA, Goodlett DR, Kruglyak L, Bedalov A. Genetic variation shapes protein networks mainly through non-transcriptional mechanisms. PLos Biol 2011; 9: e1001144
• 36 Huwiler A, Pfeilschifter J. Lipids as targets for novel anti-inflammatory therapies. Pharmacol Ther 2009; 124: 96-112
• 37 Bordoni A, Di Nunzio M, Danesi F, Biagi PL. Polyunsaturated fatty acids: from diet to binding to PPARs and other nuclear receptors. Genes Nutr 2006; 1: 95-106