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Fructose and stress induce opposite effects on lipid metabolism in the visceral adipose tissue of adult female rats through glucocorticoid action

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Abstract

Purpose

Daily exposure to stress and excessive fructose intake coincides with the growing rate of obesity and related disorders, to which women are more prone than men. Glucocorticoids, the main regulators of energy balance and response to stress, have been associated with the development of metabolic disturbances. The aim of the present study was to examine the effects of fructose overconsumption and/or chronic stress on glucocorticoid signalization and lipid metabolism in female rat adipose tissue.

Methods

We examined the effects of fructose-enriched diet and chronic unpredictable stress, separately and in combination, on glucocorticoid signaling in terms of 11β-hydroxysteroid dehydrogenase 1 (HSD1)-catalyzed corticosterone regeneration, glucocorticoid receptor (GR) intracellular distribution, hormone binding and transcriptional regulation of genes involved in lipolysis (hormone-sensitive lipase) and lipogenesis (lipoprotein lipase, acetyl-CoA carboxylase, fatty acid synthase and phosphoenolpyruvate carboxykinase) in the visceral adipose tissue (VAT) of adult female rats. Additionally, the nuclear level of the peroxisomal proliferator-activated receptor γ (PPARγ) was analyzed.

Results

The combination of stress and fructose-enriched diet led to an elevation in HSD1 expression and intracellular corticosterone concentration, whereas GR nuclear accumulation was enhanced after separate treatments. Furthermore, fructose was shown to induce the expression of all examined lipogenic genes and nuclear accumulation of PPARγ, thereby stimulating adipogenesis, while stress upregulated HSL, reducing the adipose tissue mass regardless of fructose consumption.

Conclusions

Prolonged overconsumption of fructose and chronic exposure to stress promote opposite effects on lipid metabolism in the VAT of adult female rats and suggest that these effects could be mediated by glucocorticoids.

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References

  1. Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H, Bell ME, Bhatnagar S, Laugero KD, Manalo S (2003) Chronic stress and obesity: a new view of “comfort food”. Proc Natl Acad Sci USA 100(20):11696–11701. doi:10.1073/pnas.1934666100

    Article  CAS  Google Scholar 

  2. Tappy L, Le KA (2010) Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 90(1):23–46. doi:10.1152/physrev.00019.2009

    Article  CAS  Google Scholar 

  3. Miller A, Adeli K (2008) Dietary fructose and the metabolic syndrome. Curr Opin Gastroenterol 24(2):204–209. doi:10.1097/MOG.0b013e3282f3f4c4

    Article  CAS  Google Scholar 

  4. Karagiannides I, Golovatscka V, Bakirtzi K, Sideri A, Salas M, Stavrakis D, Polytarchou C, Iliopoulos D, Pothoulakis C, Bradesi S (2014) Chronic unpredictable stress regulates visceral adipocyte-mediated glucose metabolism and inflammatory circuits in male rats. Physiol Rep 2(5):e00284. doi:10.14814/phy2.284

    Article  Google Scholar 

  5. Rosmond R (2005) Role of stress in the pathogenesis of the metabolic syndrome. Psychoneuroendocrinology 30(1):1–10. doi:10.1016/j.psyneuen.2004.05.007

    Article  CAS  Google Scholar 

  6. Shively CA, Register TC, Clarkson TB (2009) Social stress, visceral obesity, and coronary artery atherosclerosis: product of a primate adaptation. Am J Primatol 71(9):742–751. doi:10.1002/ajp.20706

    Article  Google Scholar 

  7. Matsuura N, Nagasawa K, Minagawa Y, Ito S, Sano Y, Yamada Y, Hattori T, Watanabe S, Murohara T, Nagata K (2015) Restraint stress exacerbates cardiac and adipose tissue pathology via beta-adrenergic signaling in rats with metabolic syndrome. Am J Physiol Heart Circ Physiol 308(10):H1275–H1286. doi:10.1152/ajpheart.00906.2014

    Article  CAS  Google Scholar 

  8. Fachin A, Silva RK, Noschang CG, Pettenuzzo L, Bertinetti L, Billodre MN, Peres W, Busnello F, Dalmaz C (2008) Stress effects on rats chronically receiving a highly palatable diet are sex-specific. Appetite 51(3):592–598. doi:10.1016/j.appet.2008.04.016

    Article  CAS  Google Scholar 

  9. Salehi M, Ferenczi A, Zumoff B (2005) Obesity and cortisol status. Horm Metab Res 37(4):193–197. doi:10.1055/s-2005-861374

    Article  CAS  Google Scholar 

  10. Mariniello B, Ronconi V, Rilli S, Bernante P, Boscaro M, Mantero F, Giacchetti G (2006) Adipose tissue 11beta-hydroxysteroid dehydrogenase type 1 expression in obesity and Cushing’s syndrome. Eur J Endocrinol 155(3):435–441. doi:10.1530/eje.1.02228

    Article  CAS  Google Scholar 

  11. London E, Castonguay TW (2011) High fructose diets increase 11beta-hydroxysteroid dehydrogenase type 1 in liver and visceral adipose in rats within 24-h exposure. Obesity 19(5):925–932. doi:10.1038/oby.2010.284

    Article  CAS  Google Scholar 

  12. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS (2001) A transgenic model of visceral obesity and the metabolic syndrome. Science 294(5549):2166–2170. doi:10.1126/science.1066285

    Article  CAS  Google Scholar 

  13. Wang JC, Gray NE, Kuo T, Harris CA (2012) Regulation of triglyceride metabolism by glucocorticoid receptor. Cell Biosci 2(1):19. doi:10.1186/2045-3701-2-19

    Article  CAS  Google Scholar 

  14. Vegiopoulos A, Herzig S (2007) Glucocorticoids, metabolism and metabolic diseases. Mol Cell Endocrinol 275(1–2):43–61. doi:10.1016/j.mce.2007.05.015

    Article  CAS  Google Scholar 

  15. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, Mortensen RM (1999) PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4(4):611–617

    Article  CAS  Google Scholar 

  16. Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F (2004) SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 86(11):839–848. doi:10.1016/j.biochi.2004.09.018

    Article  CAS  Google Scholar 

  17. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJ, Gakidou E (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384(9945):766–781. doi:10.1016/S0140-6736(14)60460-8

    Article  Google Scholar 

  18. Flegal KM, Carroll MD, Ogden CL, Johnson CL (2002) Prevalence and trends in obesity among US adults, 1999–2000. JAMA 288(14):1723–1727. doi:10.1001/jama.288.14.1723

    Article  Google Scholar 

  19. Freedman DS, Khan LK, Serdula MK, Galuska DA, Dietz WH (2002) Trends and correlates of class 3 obesity in the United States from 1990 through 2000. JAMA 288(14):1758–1761

    Article  Google Scholar 

  20. Tonstad SSE, Larsen PG, Thelle D (2007) Gender differences in the prevalence and determinants of the metabolic syndrome in screened subjects at risk for coronary heart disease. Metab Syndr Relat Disord 5(2):174–182

    Article  CAS  Google Scholar 

  21. Beigh SH, Jain S (2012) Prevalence of metabolic syndrome and gender differences. Bioinformation 8(13):613–616. doi:10.6026/97320630008613

    Article  Google Scholar 

  22. Joels M, Karst H, Alfarez D, Heine VM, Qin Y, van Riel E, Verkuyl M, Lucassen PJ, Krugers HJ (2004) Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus. Stress 7(4):221–231. doi:10.1080/10253890500070005

    Article  CAS  Google Scholar 

  23. Galarraga M, Campion J, Munoz-Barrutia A, Boque N, Moreno H, Martinez JA, Milagro F, Ortiz-de-Solorzano C (2012) Adiposoft: automated software for the analysis of white adipose tissue cellularity in histological sections. J Lipid Res 53(12):2791–2796. doi:10.1194/jlr.D023788

    Article  CAS  Google Scholar 

  24. Du L, Heaney AP (2012) Regulation of adipose differentiation by fructose and GluT5. Mol Endocrinol 26(10):1773–1782. doi:10.1210/me.2012-1122

    Article  CAS  Google Scholar 

  25. Legeza B, Balazs Z, Odermatt A (2014) Fructose promotes the differentiation of 3T3-L1 adipocytes and accelerates lipid metabolism. FEBS Lett 588(3):490–496. doi:10.1016/j.febslet.2013.12.014

    Article  CAS  Google Scholar 

  26. Kuo LE, Kitlinska JB, Tilan JU, Li L, Baker SB, Johnson MD, Lee EW, Burnett MS, Fricke ST, Kvetnansky R, Herzog H, Zukowska Z (2007) Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med 13(7):803–811. doi:10.1038/nm1611

    Article  CAS  Google Scholar 

  27. Michel C, Duclos M, Cabanac M, Richard D (2005) Chronic stress reduces body fat content in both obesity-prone and obesity-resistant strains of mice. Horm Behav 48(2):172–179. doi:10.1016/j.yhbeh.2005.02.004

    Article  CAS  Google Scholar 

  28. Marti O, Marti J, Armario A (1994) Effects of chronic stress on food intake in rats: influence of stressor intensity and duration of daily exposure. Physiol Behav 55(4):747–753

    Article  CAS  Google Scholar 

  29. Uchida Y, Takeshita K, Yamamoto K, Kikuchi R, Nakayama T, Nomura M, Cheng XW, Egashira K, Matsushita T, Nakamura H, Murohara T (2012) Stress augments insulin resistance and prothrombotic state: role of visceral adipose-derived monocyte chemoattractant protein-1. Diabetes 61(6):1552–1561. doi:10.2337/db11-0828

    Article  CAS  Google Scholar 

  30. Lu J, Wu XY, Zhu QB, Li J, Shi LG, Wu JL, Zhang QJ, Huang ML, Bao AM (2015) Sex differences in the stress response in SD rats. Behav Brain Res 284:231–237. doi:10.1016/j.bbr.2015.02.009

    Article  CAS  Google Scholar 

  31. Azpiroz A, Fano E, Garmendia L, Arregi A, Cacho R, Beitia G, Brain PF (1999) Effects of chronic mild stress (CMS) and imipramine administration, on spleen mononuclear cell proliferative response, serum corticosterone level and brain norepinephrine content in male mice. Psychoneuroendocrinology 24(3):345–361

    Article  CAS  Google Scholar 

  32. Kovacevic S, Nestorov J, Matic G, Elakovic I (2014) Dietary fructose-related adiposity and glucocorticoid receptor function in visceral adipose tissue of female rats. Eur J Nutr 53(6):1409–1420. doi:10.1007/s00394-013-0644-1

    Article  CAS  Google Scholar 

  33. Rask E, Olsson T, Soderberg S, Andrew R, Livingstone DE, Johnson O, Walker BR (2001) Tissue-specific dysregulation of cortisol metabolism in human obesity. J Clin Endocrinol Metab 86(3):1418–1421. doi:10.1210/jcem.86.3.7453

    Article  CAS  Google Scholar 

  34. Livingstone DE, Jones GC, Smith K, Jamieson PM, Andrew R, Kenyon CJ, Walker BR (2000) Understanding the role of glucocorticoids in obesity: tissue-specific alterations of corticosterone metabolism in obese Zucker rats. Endocrinology 141(2):560–563. doi:10.1210/endo.141.2.7297

    Article  CAS  Google Scholar 

  35. Grad I, Picard D (2007) The glucocorticoid responses are shaped by molecular chaperones. Mol Cell Endocrinol 275(1–2):2–12. doi:10.1016/j.mce.2007.05.018

    Article  CAS  Google Scholar 

  36. Crescenzo R, Bianco F, Coppola P, Mazzoli A, Valiante S, Liverini G, Iossa S (2014) Adipose tissue remodeling in rats exhibiting fructose-induced obesity. Eur J Nutr 53(2):413–419. doi:10.1007/s00394-013-0538-2

    Article  CAS  Google Scholar 

  37. Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ (2002) Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr 76(5):911–922

    CAS  Google Scholar 

  38. Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, Iwamoto K, Umesono K, Akanuma Y, Fujiwara T, Horikoshi H, Yazaki Y, Kadowaki T (1998) Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Investig 101(6):1354–1361. doi:10.1172/JCI1235

    Article  CAS  Google Scholar 

  39. Hauner H, Entenmann G, Wabitsch M, Gaillard D, Ailhaud G, Negrel R, Pfeiffer EF (1989) Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Investig 84(5):1663–1670. doi:10.1172/JCI114345

    Article  CAS  Google Scholar 

  40. Asada M, Rauch A, Shimizu H, Maruyama H, Miyaki S, Shibamori M, Kawasome H, Ishiyama H, Tuckermann J, Asahara H (2011) DNA binding-dependent glucocorticoid receptor activity promotes adipogenesis via Kruppel-like factor 15 gene expression. Lab Investig 91(2):203–215. doi:10.1038/labinvest.2010.170

    Article  CAS  Google Scholar 

  41. Steger DJ, Grant GR, Schupp M, Tomaru T, Lefterova MI, Schug J, Manduchi E, Stoeckert CJ Jr, Lazar MA (2010) Propagation of adipogenic signals through an epigenomic transition state. Genes Dev 24(10):1035–1044. doi:10.1101/gad.1907110

    Article  CAS  Google Scholar 

  42. Levert KL, Waldrop GL, Stephens JM (2002) A biotin analog inhibits acetyl-CoA carboxylase activity and adipogenesis. J Biol Chem 277(19):16347–16350. doi:10.1074/jbc.C200113200

    Article  CAS  Google Scholar 

  43. Schmid B, Rippmann JF, Tadayyon M, Hamilton BS (2005) Inhibition of fatty acid synthase prevents preadipocyte differentiation. Biochem Biophys Res Commun 328(4):1073–1082. doi:10.1016/j.bbrc.2005.01.067

    Article  CAS  Google Scholar 

  44. Franckhauser S, Munoz S, Pujol A, Casellas A, Riu E, Otaegui P, Su B, Bosch F (2002) Increased fatty acid re-esterification by PEPCK overexpression in adipose tissue leads to obesity without insulin resistance. Diabetes 51(3):624–630

    Article  CAS  Google Scholar 

  45. Lehrke M, Lazar MA (2005) The many faces of PPARgamma. Cell 123(6):993–999. doi:10.1016/j.cell.2005.11.026

    Article  CAS  Google Scholar 

  46. Brown NF, Hill JK, Esser V, Kirkland JL, Corkey BE, Foster DW, McGarry JD (1997) Mouse white adipocytes and 3T3-L1 cells display an anomalous pattern of carnitine palmitoyltransferase (CPT) I isoform expression during differentiation. Inter-tissue and inter-species expression of CPT I and CPT II enzymes. Biochem J 327(Pt 1):225–231

    Article  CAS  Google Scholar 

  47. Malandrino MI, Fucho R, Weber M, Calderon-Dominguez M, Mir JF, Valcarcel L, Escote X, Gomez-Serrano M, Peral B, Salvado L, Fernandez-Veledo S, Casals N, Vazquez-Carrera M, Villarroya F, Vendrell JJ, Serra D, Herrero L (2015) Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation. Am J Physiol Endocrinol Metab 308(9):E756–E769. doi:10.1152/ajpendo.00362.2014

    Article  Google Scholar 

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Acknowledgments

This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, Grant OI1613024, and Swiss National Science Foundation, Grant SCOPES JRP IZ73Z0_152331. The funders had no role in the design, analysis or writing of this article.

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  1. Department of Biochemistry, Institute for Biological Research “Siniša Stanković”, University of Belgrade, 142 Despot Stefan Blvd., Belgrade, 11060, Serbia

    Sanja Kovačević, Jelena Nestorov, Gordana Matić & Ivana Elaković

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  1. Sanja Kovačević
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  2. Jelena Nestorov
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Correspondence to Ivana Elaković.

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All animal procedures were in compliance with Directive 2010/63/EU on the protection of animals used for experimental and other scientific purposes, and were approved by the Ethical Committee for the Use of Laboratory Animals of the Institute for Biological Research “Siniša Stanković,” University of Belgrade. The manuscript does not contain clinical studies or patient data.

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Kovačević, S., Nestorov, J., Matić, G. et al. Fructose and stress induce opposite effects on lipid metabolism in the visceral adipose tissue of adult female rats through glucocorticoid action. Eur J Nutr 56, 2115–2128 (2017). https://doi.org/10.1007/s00394-016-1251-8

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  • DOI: https://doi.org/10.1007/s00394-016-1251-8

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