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Diet-induced obesity affects expression of adiponutrin/PNPLA3 and adipose triglyceride lipase, two members of the same family

Abstract

Background:

Adiponutrin/PNPLA3 and adipose triglyceride lipase (ATGL) are proteins highly expressed in adipose tissue which have apparently different roles (lipogenic/lipolytic). Gene expression of both proteins and their nutritional regulation have been described to be altered in genetically obese animals.

Methods:

We studied adiponutrin and ATGL expression in 6-month-old rats made obese by cafeteria diet feeding, submitted to different feeding conditions (feeding/fasting/re-feeding), compared with normoweight animals. Adiponutrin and ATGL mRNA levels were determined in white adipose tissue depots (subcutaneous and visceral) and in interscapular brown adipose tissue, and ATGL protein levels in selected depots. In addition, basal adiponutrin and ATGL expression levels were compared between 6- and 3-month-old animals.

Results:

Obesity decreased adiponutrin and ATGL expression in different adipose depots. For adiponutrin, a tendency to lower mRNA levels was observed in the white adipose depots studied in obese animals, although the decrease was only significant in the subcutaneous depot. For ATGL, a generalized and significant lower expression was found in white and brown adipose tissue of cafeteria-obese rats. When considering nutritional regulation, according to a lipogenic role, adiponutrin mRNA expression decreased with fasting and was recovered by re-feeding in normoweight animals; this regulation was lost in obese rats. Expression of the lipolytic ATGL (mRNA and protein levels) was increased by fasting in normoweight animals in the mesenteric adipose depot, while no change was evident in obese rats. Moreover, adiponutrin and ATGL nutritional regulation was affected by age, and we report a downregulation of adiponutrin mRNA basal levels with age in internal adipose depots.

Conclusions:

Cafeteria diet-induced obesity and age alter adiponutrin and ATGL expression and their regulation by feeding conditions. These results reinforce the importance of a proper expression and regulation of both proteins for body weight maintenance and their role in energy metabolism.

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References

  1. Jenkins CM, Mancuso DJ, Yan W, Sims HF, Gibson B, Gross RW . Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. J Biol Chem 2004; 279: 48968–48975.

    Article  CAS  Google Scholar 

  2. Baulande S, Lasnier F, Lucas M, Pairault J . Adiponutrin, a transmembrane protein corresponding to a novel dietary- and obesity-linked mRNA specifically expressed in the adipose lineage. J Biol Chem 2001; 276: 33336–33344.

    Article  CAS  Google Scholar 

  3. Polson DA, Thompson MP . Adiponutrin mRNA expression in white adipose tissue is rapidly induced by meal-feeding a high-sucrose diet. Biochem Biophys Res Commun 2003; 301: 261–266.

    Article  CAS  Google Scholar 

  4. Polson DA, Thompson MP . Macronutrient composition of the diet differentially affects leptin and adiponutrin mRNA expression in response to meal feeding. J Nutr Biochem 2004; 15: 242–246.

    Article  CAS  Google Scholar 

  5. Bertile F, Raclot T . Differences in mRNA expression of adipocyte-derived factors in response to fasting, refeeding and leptin. Biochim Biophys Acta 2004; 1683: 101–109.

    Article  CAS  Google Scholar 

  6. Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M et al. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 2004; 306: 1383–1386.

    Article  CAS  Google Scholar 

  7. Villena JA, Roy S, Sarkadi-Nagy E, Kim KH, Sul HS . Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J Biol Chem 2004; 279: 47066–47075.

    Article  CAS  Google Scholar 

  8. Kershaw EE, Hamm JK, Verhagen LA, Peroni O, Katic M, Flier JS . Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes 2006; 55: 148–157.

    Article  CAS  Google Scholar 

  9. Johansson LE, Hoffstedt J, Parikh H, Carlsson E, Wabitsch M, Bondeson AG et al. Variation in the adiponutrin gene influences its expression and associates with obesity. Diabetes 2006; 55: 826–833.

    Article  CAS  Google Scholar 

  10. Caimari A, Oliver P, Palou A . Regulation of adiponutrin expression by feeding conditions in rats is altered in the obese state. Obesity (Silver Spring) 2007; 15: 591–599.

    Article  CAS  Google Scholar 

  11. Lake AC, Sun Y, Li JL, Kim JE, Johnson JW, Li D et al. Expression, regulation, and triglyceride hydrolase activity of Adiponutrin family members. J Lipid Res 2005; 46: 2477–2487.

    Article  CAS  Google Scholar 

  12. Basantani MK, Sitnick MT, Cai L, Brenner DS, Gardner NP, Li JZ et al. Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome. J Lipid Res 2011; 52: 318–329.

    Article  CAS  Google Scholar 

  13. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461–1465.

    Article  CAS  Google Scholar 

  14. Kotronen A, Johansson LE, Johansson LM, Roos C, Westerbacka J, Hamsten A et al. A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans. Diabetologia 2009; 52: 1056–1060.

    Article  CAS  Google Scholar 

  15. Tian C, Stokowski RP, Kershenobich D, Ballinger DG, Hinds DA . Variant in PNPLA3 is associated with alcoholic liver disease. Nat Genet 2010; 42: 21–23.

    Article  CAS  Google Scholar 

  16. He S, McPhaul C, Li JZ, Garuti R, Kinch L, Grishin NV et al. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. J Biol Chem 2010; 285: 6706–6715.

    Article  CAS  Google Scholar 

  17. Haemmerle G, Lass A, Zimmermann R, Gorkiewicz G, Meyer C, Rozman J et al. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science 2006; 312: 734–737.

    Article  CAS  Google Scholar 

  18. Kralisch S, Klein J, Lossner U, Bluher M, Paschke R, Stumvoll M et al. Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes. Mol Cell Endocrinol 2005; 240: 43–49.

    Article  CAS  Google Scholar 

  19. Caimari A, Oliver P, Palou A . Impairment of nutritional regulation of adipose triglyceride lipase expression with age. Int J Obes (Lond) 2008; 32: 1193–1200.

    Article  CAS  Google Scholar 

  20. Deiuliis JA, Shin J, Bae D, Azain MJ, Barb R, Lee K . Developmental, hormonal, and nutritional regulation of porcine adipose triglyceride lipase (ATGL). Lipids 2008; 43: 215–225.

    Article  CAS  Google Scholar 

  21. Hardie LJ, Rayner DV, Holmes S, Trayhurn P . Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. Biochem Biophys Res Commun 1996; 223: 660–665.

    Article  CAS  Google Scholar 

  22. Matamala JC, Gianotti M, Pericas J, Quevedo S, Roca P, Palou A et al. Changes induced by fasting and dietetic obesity in thermogenic parameters of rat brown adipose tissue mitochondrial subpopulations. Biochem J 1996; 319 (Part 2): 529–534.

    Article  CAS  Google Scholar 

  23. Pico C, Sanchez J, Oliver P, Palou A . Leptin production by the stomach is up-regulated in obese (fa/fa) Zucker rats. Obes Res 2002; 10: 932–938.

    Article  CAS  Google Scholar 

  24. Johansson LE, Lindblad U, Larsson CA, Rastam L, Ridderstrale M . Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity. Eur J Endocrinol 2008; 159: 577–583.

    Article  CAS  Google Scholar 

  25. Von Diemen V, Trindade EN, Trindade MR . Experimental model to induce obesity in rats. Acta Cir Bras 2006; 21: 425–429.

    Article  Google Scholar 

  26. Berraondo B, Marti A, Duncan JS, Trayhurn P, Martinez JA . Up-regulation of muscle UCP2 gene expression by a new beta3-adrenoceptor agonist, trecadrine, in obese (cafeteria) rodents, but down-regulation in lean animals. Int J Obes Relat Metab Disord 2000; 24: 156–163.

    Article  CAS  Google Scholar 

  27. Berraondo B, Martinez JA . Free fatty acids are involved in the inverse relationship between hormone-sensitive lipase (HSL) activity and expression in adipose tissue after high-fat feeding or beta3-adrenergic stimulation. Obes Res 2000; 8: 255–261.

    Article  CAS  Google Scholar 

  28. Lopez IP, Marti A, Milagro FI, Zulet Md Mde L, Moreno-Aliaga MJ, Martinez JA et al. DNA microarray analysis of genes differentially expressed in diet-induced (cafeteria) obese rats. Obes Res 2003; 11: 188–194.

    Article  CAS  Google Scholar 

  29. Rodriguez AM, Palou A . Uncoupling proteins: gender dependence and their relation to body weight control. Int J Obes Relat Metab Disord 2004; 28: 500–502.

    Article  CAS  Google Scholar 

  30. Ribot J, Rodriguez AM, Rodriguez E, Palou A . Adiponectin and resistin response in the onset of obesity in male and female rats. Obesity (Silver Spring) 2008; 16: 723–730.

    Article  CAS  Google Scholar 

  31. Mercader J, Granados N, Caimari A, Oliver P, Bonet ML, Palou A . Retinol-binding protein 4 and nicotinamide phosphoribosyltransferase/visfatin in rat obesity models. Horm Metab Res 2008; 40: 467–472.

    Article  CAS  Google Scholar 

  32. Caimari A, Oliver P, Rodenburg W, Keijer J, Palou A . Slc27a2 expression in peripheral blood mononuclear cells as a molecular marker for overweight development. Int J Obes (Lond) 2010; 34: 831–839.

    Article  CAS  Google Scholar 

  33. Giorgino F, Laviola L, Eriksson JW . Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies. Acta Physiol Scand 2005; 183: 13–30.

    Article  CAS  Google Scholar 

  34. Boden G . Free fatty acids (FFA), a link between obesity and insulin resistance. Front Biosci 1998; 3: d169–d175.

    Article  CAS  Google Scholar 

  35. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  36. Sanchez J, Palou A, Pico C . Response to carbohydrate and fat refeeding in the expression of genes involved in nutrient partitioning and metabolism: striking effects on fibroblast growth factor-21 induction. Endocrinology 2009; 150: 5341–5350.

    Article  CAS  Google Scholar 

  37. Palou M, Priego T, Sanchez J, Rodriguez AM, Palou A, Pico C . Gene expression patterns in visceral and subcutaneous adipose depots in rats are linked to their morphologic features. Cell Physiol Biochem 2009; 24: 547–556.

    Article  CAS  Google Scholar 

  38. Caimari A, Oliver P, Rodenburg W, Keijer J, Palou A . Feeding conditions control the expression of genes involved in sterol metabolism in peripheral blood mononuclear cells of normoweight and diet-induced (cafeteria) obese rats. J Nutr Biochem 2010; 21: 1127–1133.

    Article  CAS  Google Scholar 

  39. Livak KJ, Schmittgen TD . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001; 25: 402–408.

    Article  CAS  Google Scholar 

  40. Oliver P, Pico C, Palou A . Ontogenesis of leptin expression in different adipose tissue depots in the rat. Pflugers Arch 2001; 442: 383–390.

    Article  CAS  Google Scholar 

  41. Oliver P, Pico C, Serra F, Palou A . Resistin expression in different adipose tissue depots during rat development. Mol Cell Biochem 2003; 252: 397–400.

    Article  CAS  Google Scholar 

  42. Oliver P, Ribot J, Rodriguez AM, Sanchez J, Pico C, Palou A . Resistin as a putative modulator of insulin action in the daily feeding/fasting rhythm. Pflugers Arch 2006; 452: 260–267.

    Article  CAS  Google Scholar 

  43. Sanchez J, Oliver P, Pico C, Palou A . Diurnal rhythms of leptin and ghrelin in the systemic circulation and in the gastric mucosa are related to food intake in rats. Pflugers Arch 2004; 448: 500–506.

    Article  CAS  Google Scholar 

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Acknowledgements

CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of the ISCIII. This work was supported by the Spanish Government (Ministerio de Educación y Ciencia, AGL 2009-11277/ALI). Our Laboratory is a member of the European Research Network of Excellence NuGO (The European Nutrigenomics Organization, EU Contract: FOOD-CT-2004-506360 NUGO).

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Correspondence to A Palou.

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Oliver, P., Caimari, A., Díaz-Rúa, R. et al. Diet-induced obesity affects expression of adiponutrin/PNPLA3 and adipose triglyceride lipase, two members of the same family. Int J Obes 36, 225–232 (2012). https://doi.org/10.1038/ijo.2011.92

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