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The differential effects of high-fat and high- -fructose diets on the liver of male albino rat and the proposed underlying mechanisms
Affiliations- Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt
- Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia
open access
Abstract
Background: The Western-style diet is characterised by the high intake of energy- -dense foods. Consumption of either high-fructose diet or saturated fat resulted in the development of metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Many researchers studied the effect of high-fat diet (HFD), high-fructose diet (HFruD) and high-fructose high-fat diet (HFHF) on the liver. The missing data are the comparison effect of these groups i.e. are effects of the HFHF diet on the liver more pronounced? So, this study was designed to compare the metabolic and histopathological effect of the HFD, HFruD, and HFHF on the liver. The proposed underlying mechanisms involved in these changes were also studied.
Materials and methods: Twenty four rats were divided into four groups: con- trol, HFD, HFruD, and HFHF. Food was offered for 6 weeks. Biochemical, light microscopic, immunohistochemical (Inducible nitric oxide synthase [iNOS] and alpha-smooth muscle actin [α-SMA]), real-time polymerase chain reaction (gene expression of TNF-α, interleukin-6, Bax, BCL-2, and caspase 3), histomorphometric analysis and oxidative/antioxidative markers (thiobarbituric acid reactive substances [TBARS], malondialdehyde [MDA]/glutathione [GSH] and superoxide dismutase [SOD]) were done.
Results: The HFD, HFruD and HFHF groups developed a cluster of liver disorders; steatosis, necrosis, inflammation, apoptosis, ballooning degeneration and cytopla- smic vacuolations. Internal metabolic impairments include elevated serum levels of glucose, triglycerides, low density lipoprotein and decreased serum levels of high density lipoprotein and albumin. The immunoreaction of the α-SMA and iNOS was strong in these groups. The oxidant markers (MDA and TBARS) were elevated, while the antioxidant markers (SOD and GSH) were decreased. The area per cent of collagen, inflammatory markers, caspase 3 and Bax were elevated, while the BCL-2/Bax ratio was decreased. The decrease in PAS, antioxidant markers and the elevation of the α-SMA, iNOS, inflammatory and oxidant markers were obvious in the HFHF when compared to that of the other groups.
Conclusions: High-fat diet, HFruD, and HFHF developed morphologic hepatic changes ranging from steatosis to necrosis and inflammation, besides the deve- lopment of internal metabolic impairments. The chief factors of hepatic injury were fat accumulation in the hepatocytes, oxidative stress and highly elevated iNOS. Compared to the other groups, HFHF’s effect was more prominent.
Abstract
Background: The Western-style diet is characterised by the high intake of energy- -dense foods. Consumption of either high-fructose diet or saturated fat resulted in the development of metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Many researchers studied the effect of high-fat diet (HFD), high-fructose diet (HFruD) and high-fructose high-fat diet (HFHF) on the liver. The missing data are the comparison effect of these groups i.e. are effects of the HFHF diet on the liver more pronounced? So, this study was designed to compare the metabolic and histopathological effect of the HFD, HFruD, and HFHF on the liver. The proposed underlying mechanisms involved in these changes were also studied.
Materials and methods: Twenty four rats were divided into four groups: con- trol, HFD, HFruD, and HFHF. Food was offered for 6 weeks. Biochemical, light microscopic, immunohistochemical (Inducible nitric oxide synthase [iNOS] and alpha-smooth muscle actin [α-SMA]), real-time polymerase chain reaction (gene expression of TNF-α, interleukin-6, Bax, BCL-2, and caspase 3), histomorphometric analysis and oxidative/antioxidative markers (thiobarbituric acid reactive substances [TBARS], malondialdehyde [MDA]/glutathione [GSH] and superoxide dismutase [SOD]) were done.
Results: The HFD, HFruD and HFHF groups developed a cluster of liver disorders; steatosis, necrosis, inflammation, apoptosis, ballooning degeneration and cytopla- smic vacuolations. Internal metabolic impairments include elevated serum levels of glucose, triglycerides, low density lipoprotein and decreased serum levels of high density lipoprotein and albumin. The immunoreaction of the α-SMA and iNOS was strong in these groups. The oxidant markers (MDA and TBARS) were elevated, while the antioxidant markers (SOD and GSH) were decreased. The area per cent of collagen, inflammatory markers, caspase 3 and Bax were elevated, while the BCL-2/Bax ratio was decreased. The decrease in PAS, antioxidant markers and the elevation of the α-SMA, iNOS, inflammatory and oxidant markers were obvious in the HFHF when compared to that of the other groups.
Conclusions: High-fat diet, HFruD, and HFHF developed morphologic hepatic changes ranging from steatosis to necrosis and inflammation, besides the deve- lopment of internal metabolic impairments. The chief factors of hepatic injury were fat accumulation in the hepatocytes, oxidative stress and highly elevated iNOS. Compared to the other groups, HFHF’s effect was more prominent.
Keywords
high-fat diet; high-fructose diet; high fructose high-fat diet; liver
About this articleTitle
The differential effects of high-fat and high- -fructose diets on the liver of male albino rat and the proposed underlying mechanisms
Journal
Issue
Article type
Original article
Pages
124-136
Published online
2018-07-06
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3358
Article views/downloads
2553
DOI
Pubmed
Bibliographic record
Folia Morphol 2019;78(1):124-136.
Keywords
high-fat diet
high-fructose diet
high fructose high-fat diet
liver
Authors
S. M. Zaki
S. A. Fattah
D. S. Hassan
References (41)- Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science. 1998; 281(5381): 1322–1326.
- Alberti KG, Eckel RH, Grundy SM, et al. International Diabetes Federation Task Force on Epidemiology and Prevention, Hational Heart, Lung, and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity. 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(16): 1640–1645.
- Angulo P, Lindor KD. Non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2002; 17(Suppl): S186–S190.
- Asakawa T, Yagi M, Tanaka Y, et al. The herbal medicine Inchinko-to reduces hepatic fibrosis in cholestatic rats. Pediatr Surg Int. 2012; 28(4): 379–384.
- Birben E, Sahiner U, Sackesen C, et al. Oxidative stress and antioxidant defense. World Allergy Organization J. 2012; 5(1): 9–19.
- Bocarsly ME, Powell ES, Avena NM, et al. High-fructose corn syrup causes characteristics of obesity in rats: increased body weight, body fat and triglyceride levels. Pharmacol Biochem Behav. 2010; 97(1): 101–106.
- Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004; 114(2): 147–152.
- Collins S, Martin TL, Surwit RS, et al. Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics. Physiol Behav. 2004; 81(2): 243–248.
- Collison KS, Zaidi MZ, Saleh SM, et al. Effect of trans-fat, fructose and monosodium glutamate feeding on feline weight gain, adiposity, insulin sensitivity, adipokine and lipid profile. Br J Nutr. 2011; 106(2): 218–226.
- Costa E, Rezende B, Cortes S, et al. Neuronal Nitric Oxide Synthase in Vascular Physiology and Diseases. Front Physiol. 2016; 7.
- Day CP, James OF. Hepatic steatosis: innocent bystander or guilty party? Hepatology. 1998; 27(6): 1463–1466.
- Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology. 1998; 114(4): 842–845.
- Dröge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002; 82(1): 47–95.
- Feldstein A, Gores G. Steatohepatitis and apoptosis: therapeutic implications. Am J Gastroenterol. 2004; 99(9): 1718–1719.
- Feldstein A, Canbay A, Angulo P, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003; 125(2): 437–443.
- Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957; 26(1): 497–509.
- Ha SK, Chae C. Inducible nitric oxide distribution in the fatty liver of a mouse with high fat diet-induced obesity. Exp Anim. 2010; 59(5): 595–604.
- Hebbard L, George J. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2011; 8(1): 35–44.
- Jurdak N, Lichtenstein AH, Kanarek RB. Diet-induced obesity and spatial cognition in young male rats. Nutr Neurosci. 2008; 11(2): 48–54.
- Larter CZ, Yeh MM. Animal models of NASH: getting both pathology and metabolic context right. J Gastroenterol Hepatol. 2008; 23(11): 1635–1648.
- Lee JS, Jun DW, Kim EK, et al. Histologic and metabolic derangement in high-fat, high-fructose, and combination diet animal models. ScientificWorldJournal. 2015; 2015: 306326.
- Li S, Liao X, Meng F, et al. Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats. PLoS One. 2014; 9(1): e86724.
- Ma J, Zou C, Guo L, et al. Novel Death Defying Domain in Met entraps the active site of caspase-3 and blocks apoptosis in hepatocytes. Hepatology. 2014; 59(5): 2010–2021.
- Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009; 49(6): 1877–1887.
- Pereira-Lancha LO, Campos-Ferraz PL, Lancha AH. Obesity: considerations about etiology, metabolism, and the use of experimental models. Diabetes Metab Syndr Obes. 2012; 5: 75–87.
- Peverill W, Powell LW, Skoien R. Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation. Int J Mol Sci. 2014; 15(5): 8591–8638.
- Ribeiro PS, Cortez-Pinto H, Solá S, et al. Hepatocyte apoptosis, expression of death receptors, and activation of NF-kappaB in the liver of nonalcoholic and alcoholic steatohepatitis patients. Am J Gastroenterol. 2004; 99(9): 1708–1717.
- Rolo AP, Teodoro JS, Palmeira CM. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic Biol Med. 2012; 52(1): 59–69.
- Schwartz DM, Wolins NE. A simple and rapid method to assay triacylglycerol in cells and tissues. J Lipid Res. 2007; 48(11): 2514–2520.
- Sheehan DC, Hrapchak BB. Theory and practice of histotechnology. 2d edn. Mosby, St Louis 1980.
- Spruss A, Kanuri G, Wagnerberger S, et al. Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology. 2009; 50(4): 1094–1104.
- Stark AH, Timar B, Madar Z. Adaptation of Sprague Dawley rats to long-term feeding of high fat or high fructose diets. Eur J Nutr. 2000; 39(5): 229–234.
- Takaki A, Kawai D, Yamamoto K. Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH). Int J Mol Sci. 2013; 14(10): 20704–20728.
- Teli MR, James OF, Burt AD, et al. The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology. 1995; 22(6): 1714–1719.
- Thornberry NA, Lazebnik Y. Caspases: enemies within. Science. 1998; 281(5381): 1312–1316.
- Tipple TE, Rogers LK. Methods for the determination of plasma or tissue glutathione levels. Methods Mol Biol. 2012; 889: 315–324.
- Tsujimoto Y. Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria? Genes to Cells. 1998; 3(11): 697–707.
- Wang MY, Grayburn P, Chen S, et al. Adipogenic capacity and the susceptibility to type 2 diabetes and metabolic syndrome. Proc Natl Acad Sci U S A. 2008; 105(16): 6139–6144.
- Wang Y, Ausman LM, Russell RM, et al. Increased apoptosis in high-fat diet-induced nonalcoholic steatohepatitis in rats is associated with c-Jun NH2-terminal kinase activation and elevated proapoptotic Bax. J Nutr. 2008; 138(10): 1866–1871.
- Weydert CJ, Cullen JJ. Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue. Nat Protoc. 2010; 5(1): 51–66.
- Woodie L, Blythe S. The differential effects of high-fat and high-fructose diets on physiology and behavior in male rats. Nutr Neurosci. 2018; 21(5): 328–336.
