Abstract
Purpose
To explore the effect of a fructose-rich diet on morphological and functional changes in white adipose tissue (WAT) that could contribute to the development of insulin resistance.
Methods
Adult sedentary rats were fed a fructose-rich diet for 8 weeks. Glucose tolerance test was carried out together with measurement of plasma triglycerides, non-esterified fatty acids and lipid peroxidation. In subcutaneous abdominal and intra-abdominal WAT, number and size of adipocytes together with cellular insulin sensitivity and lipolytic activity were assessed.
Results
Rats fed a fructose-rich diet exhibited a significant increase in plasma insulin, triglycerides, non-esterified fatty acids and lipid peroxidation, together with significantly increased body lipids and epididymal and mesenteric WAT, compared to controls. Mean adipocyte volume in subcutaneous abdominal WAT was significantly lower, while mean adipocyte volume in intra-abdominal WAT was significantly higher, in rats fed a fructose-rich diet compared to controls. A significant increase in larger adipocytes and a significant decrease in smaller adipocytes were found in intra-abdominal WAT in rats fed a fructose-rich diet compared to controls. Insulin’s ability to inhibit lipolysis was blunted in subcutaneous abdominal and intra-abdominal adipocytes from fructose-fed rats. Accordingly, lower p-Akt/Akt ratio was found in WAT in rats fed a fructose-rich diet compared to controls.
Conclusions
Long-term consumption of high levels of fructose elicits remarkable morphological and functional modifications, particularly in intra-abdominal WAT, that are highly predictive of obesity and insulin resistance and that contribute to the worsening of metabolic alterations peculiar in a fructose-rich, hypolipidic diet.
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References
Olefsky JM, Glass CK (2010) Macrophages, inflammation, and insulin resistance. Ann Rev Physiol 72:219–246
Cascio G, Schiera G, Di Liegro I (2012) Dietary fatty acids in metabolic syndrome, diabetes and cardiovascular diseases. Curr Diabetes Rev 8(1):2–17
Strable MS, Ntambi JM (2010) Genetic control of de novo lipogenesis: role in diet-induced obesity. Crit Rev Biochem Mol Biol 45(3):199–214
Crescenzo R, Bianco F, Falcone I, Coppola P, Liverini G, Iossa S (2013) Increased hepatic de novo lipogenesis and mitochondrial efficiency in a model of obesity induced by diets rich in fructose. Eur J Nutr 52:1537–1545
Crescenzo R, Bianco F, Falcone I, Prisco M, Liverini G, Iossa S (2008) Alterations in hepatic mitochondrial compartment in a model of obesity and insulin resistance. Obesity 16(5):958–964
Lionetti L, Mollica MP, Crescenzo R, D’Andrea E, Ferraro M, Bianco F, Liverini G, Iossa S (2007) Skeletal muscle subsarcolemmal mitochondrial dysfunction in high-fat fed rats exhibiting impaired glucose homeostasis. Int J Obes 31:1596–1604
Item F, Konrad D (2012) Visceral fat and metabolic inflammation: the portal theory revisited. Obes Rev 13:30–39
Fernandes MAS, Custodio JBA, Santos MS et al (2006) Tetrandrine concentrations not affecting oxidative phosphorylation protect rat liver mitochondria from oxidative stress. Mitochondrion 6:176–185
Folch J, Lees M, Stanley GHS (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–510
Crescenzo R, Bianco F, Falcone I, Prisco M, Dulloo AG, Liverini G, Iossa S (2010) Hepatic mitochondrial energetics during catch-up fat after caloric restriction. Metabolism 59:1221–1230
Gundersen HJG (2002) The smooth fractionators. J Microsc 207:191–210
Wang T, Si Y, Shirihai OS, Si H, Schultz V, Corkey RF, Hu L, Deeney JT, Guo W, Corkey BE (2010) Respiration in adipocytes is inhibited by reactive oxygen species. Obesity 18:1493–1502
Hardy OT, Czech MP, Corvera S (2012) What causes the insulin resistance underlying obesity? Curr Opin Endocrinol Diabetes Obes 19(2):81–87
Samuel VT (2011) Fructose induced lipogenesis: from sugar to fat to insulin resistance. Trends Endocrinol Metab 22(2):60–65
Tappy L, Le KE (2010) Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev 90:23–46
Stanhope KL, Havel PJ (2008) Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance. Curr Opin Lipidol 19:16–24
Delbosc S, Paizanis E, Magous R, Araiz C, Dimo T, Cristol JP, Cros G, Azay J (2005) Involvement of oxidative stress and NADPH oxidase activation in the development of cardiovascular complications in a model of insulin resistance, the fructose-fed rat. Atherosclerosis 179(1):43–49
Marcelino H, Veyrat-Durebex C, Summermatter S, Sarafian D, Miles-Chan J, Arsenijevic D, Zani F, Montani JP, Seydoux J, Solinas G, Rohner-Jeanrenaud F, Dulloo AG (2013) A role for adipose tissue de novo lipogenesis in glucose homeostasis during catch-up growth: a Randle cycle favoring fat storage. Diabetes 62(2):362–372
Wronska A, Kmiec Z (2012) Structural and biochemical characteristics of various white adipose tissue depots. Acta Physiol 205:194–208
DiGirolamo M, Fine JB, Tagra K, Rossmanith R (1998) Qualitative regional differences in adipose tissue growth and cellularity in male Wistar rats fed ad libitum. Am J Physiol 274:R1460–R1467
Lee MJ, Wu Y, Fried SK (2012) Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Aspects Med. doi:10.1016/j.mam.2012.10.001
Lundgren M, Svensson M, Lindmark S, Renstrom F, Ruge T, Eriksson JW (2007) Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’. Diabetologia 50:625–633
Ibrahim MM (2010) Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev 11:11–18
Berger JJ, Barnard RJ (1999) Effect of diet on fat cell size and hormone-sensitive lipase activity. J Appl Physiol 87(1):227–232
Wueest S, Rapold RA, Rytka JM, Schoenle EJ, Konrad D (2009) Basal lipolysis, not the degree of insulin resistance, differentiates large from small isolated adipocytes in high-fat fed mice. Diabetologia 52:541–546
Soria A, D’Alessandro MA, Lombardo YB (2001) Duration of feeding on a sucrose rich diet determines metabolic and morphological changes in rat adipocytes. J Appl Physiol 91:2109–2116
Arner P (2005) Human fat cell lipolysis: biochemistry, regulation and clinical role. Best Pract Res Clin Endocrinol Metab 19:471–482
Martins AR, Nachbar RT, Gorjao R, Vinolo MA, Festuccia WT, Lambertucci RH, Cury-Boaventura MF, Silveira LR, Curi R, Hirabara SR (2012) Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function. Lipids Health Dis 11:30–41
Chaveza JA, Summers SA (2010) Lipid oversupply, selective insulin resistance, and lipotoxicity: molecular mechanisms. Biochim Biophys Acta 1801(3):252–265
Acknowledgments
This work was supported by a grant from University “Federico II” of Naples and by P.O.R. Campania FSE 2007-2013, Project CREME. The authors thank Dr. Emilia De Santis for skillful management of animal housing.
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The authors declare no conflict of interest.
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Crescenzo, R., Bianco, F., Coppola, P. et al. Adipose tissue remodeling in rats exhibiting fructose-induced obesity. Eur J Nutr 53, 413–419 (2014). https://doi.org/10.1007/s00394-013-0538-2
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DOI: https://doi.org/10.1007/s00394-013-0538-2