Research Article
Molecular, biochemical, and histopathological effects of long-term low and high-percentage fructose consumption on the liver in rats
Abstract
The aim of this study was to investigate the lipogenic and inflammatory effects of low and high percentage fructose solutions in rats. Wistar albino rats were fed with fructose solutions for 10 weeks. The groups were as follows: Cont (Control), F15 (Fructose 15%), F30 (Fructose 30%), and F60 (Fructose 60%). Rats' body weights were measured weekly. Also, lipogenic and inflammatory gene expression levels, biochemical parameters, and histopathological changes in the liver were investigated. After 10 weeks, it was observed that the animals in the F60 were the heaviest, while the animals in the F30 were the lightest. In all experimental groups, triglycerides were significantly higher than those of controls (P<0.05). In F30 and F60, TNFα, IL-6, and IL-1β were upregulated in the liver compared to control (P<0.05). In addition, SREBP-1c, ChREBP, FAS, ACACA, and SCD-1 were upregulated in all fructose feeding groups compared to Cont (P<0.05). The livers of rats in the F30 and F60 groups had degenerative changes and steatosis. The most detrimental effects of fructose were observed in F60. The concentration of fructose was found to be a very important factor for maintaining normal liver physiology at the molecular level.
Keywords
Supporting Institution
This study was financially supported by TUBITAK with 118O381 project number.
Project Number
118O381
References
- Ayala A, Muñoz MF, Argüelles S (2014): Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev, 360438.
- Batista LO, Ramos VW, Rosas Fernández MA, et al (2019): Oral solution of fructose promotes SREBP-1c high-expression in the hypothalamus of Wistar rats. Nutr Neurosci, 22, 648-654.
- Berköz M, Yalın S (2008): Yağ Dokusunun İmmünolojik ve İnflamatuvar Fonksiyonları. Mers Üni Sağ Bil Derg, 1, 1-8.
- Castro MC, Massa ML, Arbeláez LG, et al (2015): Fructose-induced inflammation, insulin resistance and oxidative stress: A liver pathological triad effectively disrupted by lipoic acid. Life Sci, 137, 1-6.
- Cha JY, Repa JJ (2007): The liver X receptor (LXR) and hepatic lipogenesis The carbohydrate-response element-binding protein is a target gene of LXR. J Biol Chem, 282, 743-751.
- Chakravarthy MV, Pan Z, Zhu Y, et al (2005): “New” hepatic fat activates PPARα to maintain glucose, lipid, and cholesterol homeostasis. Cell Metab, 1, 309-322.
- de Moura RF, Ribeiro C, de Oliveira JA, et al (2018): Metabolic syndrome signs in Wistar rats submitted to different high-fructose ingestion protocols. Br J Nutr, 101, 1178-1184.
- dos Santos BP, da Costa Diesel LF, da Silva Meirelles L, et al (2016): Identification of suitable reference genes for quantitative gene expression analysis in rat adipose stromal cells induced to trilineage differentiation. Gene, 594, 211-219.
- Feldstein AE, Werneburg NW, Canbay A, et al (2004): Free fatty acids promote hepatic lipotoxicity by stimulating TNF‐α expression via a lysosomal pathway. Hepatology, 40, 185-194.
- Geidl-Flueck B, Gerber PA (2017): Insights into the hexose liver metabolism-Glucose versus fructose. Nutrients, 9, 1026.
- Gou SH, Huang HF, Chen XY, et al (2016): Lipid-lowering, hepatoprotective, and atheroprotective effects of the mixture Hong-Qu and gypenosides in hyperlipidemia with NAFLD rats. J Chinese Med Assoc, 79, 111-121.
- Güvenç M, Cellat M, Gökçek İ, et al (2020): Nobiletin attenuates acetaminophen‐induced hepatorenal toxicity in rats. J Biochem Mol Toxicol, 34, e224-227.
- He Z, Jiang T, Wang Z, et al (2004): Modulation of carbohydrate response element-binding protein gene expression in 3T3-L1 adipocytes and rat adipose tissue. Am J Physiol Metab, 287, E424-430.
- Herman MA, Samuel VT (2016): The sweet path to metabolic demise: fructose and lipid synthesis. Trends Endocrinol Metab, 27, 719-730.
- Hirahatake KM, Meissen JK, Fiehn O, et al (2011): Comparative effects of fructose and glucose on lipogenic gene expression and intermediary metabolism in HepG2 liver cells. PLoS One, 6, e26583.
- Janevski M, Ratnayake S, Siljanovski S, et al (2012): Fructose containing sugars modulate mRNA of lipogenic genes ACC and FAS and protein levels of transcription factors ChREBP and SREBP1c with no effect on body weight or liver fat. Food Funct, 3, 141-149.
- Jegatheesan P, Beutheu S, Ventura G, et al (2015); Citrulline and nonessential amino acids prevent fructose-induced nonalcoholic fatty liver disease in rats. J Nutr, 145, 2273-2279.
- Kanuri G, Spruss A, Wagnerberger S, et al (2011): Role of tumor necrosis factor α (TNFα) in the onset of fructose-induced nonalcoholic fatty liver disease in mice. J Nutr Biochem, 22, 527-534.
- Khan HA, Abdelhalim MA, Alhomida AS, et al (2013):Transient increase in IL-1β, IL-6 and TNF-α gene expression in rat liver exposed to gold nanoparticles. Genet Mol Res, 12, 5851-5857.
- Koo HY, Wallig MA, Chung BH, et al (2008): Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liver. Biochim Biophys Acta (BBA)-Molecular Basis Dis, 1782, 341-348.
- Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods, 25, 402–408.
- Lozano I, Van der Werf R, Bietiger W, et al (2016): High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications. Nutr Metab (Lond), 13, 15.
- Luna LG (1968): Manual of histologic staining methods of the Armed Forces Institute of Pathology. McGraw-Hill, New York.
- Matsusue K, Aibara D, Hayafuchi R, et al (2014): Hepatic PPARγ and LXRα independently regulate lipid accumulation in the livers of genetically obese mice. FEBS Lett, 588, 2277-2281.
- Miyazaki M, Dobrzyn A, Man WC, et al (2004): Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and-independent mechanisms. J Biol Chem, 279, 25164-25171.
- Mock K, Lateef S, Benedito VA, et al (2017): High-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulation. J Nutr Biochem, 39, 32-39.
- Mohammadi E, Ghaedi K, Esmailie A, et al (2013): Gene expression profiling of liver X receptor α and Bcl-2-associated X protein in experimental transection spinal cord-injured rats. J Spinal Cord Med, 36, 66-71.
- Ntambi JM, Miyazaki M (2003): Recent insights into stearoyl-CoA desaturase-1. Curr Opin Lipidol, 14, 255-261.
- Ode KL, Frohnert BI, Nathan BM (2009): Identification and treatment of metabolic complications in pediatric obesity. Rev Endocr Metab Disord, 10, 167-188.
- Ouyang X, Cirillo P, Sautin Y, et al (2008): Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol, 48, 993-999.
- Ozkan H, Yakan A (2019): Dietary high calories from sunflower oil, sucrose and fructose sources alters lipogenic genes expression levels in liver and skeletal muscle in rats. Ann Hepatol, 18, 15-24.
- Rio DC, Ares M, Hannon GJ, et al (2010): Purification of RNA using TRIzol (TRI reagent). Cold Spring Harb Protoc, 5439.
- Softic S, Cohen DE, Kahn CR (2016): Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Dig Dis Sci, 61, 1282-1293.
- Softic S, Gupta MK, Wang GX, et al (2017): Divergent effects of glucose and fructose on hepatic lipogenesis and insulin signaling. J Clin Invest, 127, 4059-4074.
- Tappy L, Lê KA (2010): Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev, 90, 23-46.
- Vasiljević A, Bursać B, Djordjevic A, et al (2014): Hepatic inflammation induced by high-fructose diet is associated with altered 11βHSD1 expression in the liver of Wistar rats. Eur J Nutr, 53, 1393-1402.
- Yasari S, Prud’homme D, Wang D, et al (2010): Exercise training decreases hepatic SCD-1 gene expression and protein content in rats. Mol Cell Biochem, 335, 291-299.
Ratlarda uzun süreli düşük ve yüksek doz fruktoz tüketiminin karaciğerde moleküler, biyokimyasal ve histopatolojik etkileri
Abstract
Diyetlerdeki karbonhidrat çeşitleri hakkında bilimsel tartışmalar devam etmektedir. Fruktoz, gıda ürünlerinde yaygın olarak kullanılmaktadır. Çalışmada, ratlarda düşük ve yüksek fruktoz solüsyonlarının lipogenik ve inflamatuar etkileri araştırılmıştır. Hayvanlar, 10 hafta süreyle fruktoz solüsyonları ile beslenmiştir. Gruplar: Con (Kontrol), F15 (Fruktoz %15), F30 (Fruktoz %30), F60 (Fruktoz %60) şeklinde olmuştur. F60 en hafif grupken, F30 en ağır grup olarak belirlenmiştir. Trigliserit seviyeleri tüm deneme gruplarında Con'dan önemli ölçüde daha yüksek olmuştur (P<0,05). F30 ve F60'da, TNFα, IL-6 ve IL-1β’nın karaciğerde upregüle olduğu belirlenmiştir (P<0,05). Bununla birlikte tüm fruktoz gruplarında SREBP-1c, ChREBP, FAS, ACACA ve SCD-1 upregüle olmuştur (P<0,05). F30 ve F60 gruplarının karaciğerlerinde dejeneratif değişiklikler ve steatoz belirlenmiştir. Fruktozun en zararlı etkileri F60 grubunda belirlenmiştir. Fruktoz konsantrasyonunun, normal karaciğer fizyolojisini moleküler seviyelerde sürdürmek için çok önemli bir faktör olduğu belirlenmiştir.
Keywords
Project Number
118O381
References
- Ayala A, Muñoz MF, Argüelles S (2014): Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev, 360438.
- Batista LO, Ramos VW, Rosas Fernández MA, et al (2019): Oral solution of fructose promotes SREBP-1c high-expression in the hypothalamus of Wistar rats. Nutr Neurosci, 22, 648-654.
- Berköz M, Yalın S (2008): Yağ Dokusunun İmmünolojik ve İnflamatuvar Fonksiyonları. Mers Üni Sağ Bil Derg, 1, 1-8.
- Castro MC, Massa ML, Arbeláez LG, et al (2015): Fructose-induced inflammation, insulin resistance and oxidative stress: A liver pathological triad effectively disrupted by lipoic acid. Life Sci, 137, 1-6.
- Cha JY, Repa JJ (2007): The liver X receptor (LXR) and hepatic lipogenesis The carbohydrate-response element-binding protein is a target gene of LXR. J Biol Chem, 282, 743-751.
- Chakravarthy MV, Pan Z, Zhu Y, et al (2005): “New” hepatic fat activates PPARα to maintain glucose, lipid, and cholesterol homeostasis. Cell Metab, 1, 309-322.
- de Moura RF, Ribeiro C, de Oliveira JA, et al (2018): Metabolic syndrome signs in Wistar rats submitted to different high-fructose ingestion protocols. Br J Nutr, 101, 1178-1184.
- dos Santos BP, da Costa Diesel LF, da Silva Meirelles L, et al (2016): Identification of suitable reference genes for quantitative gene expression analysis in rat adipose stromal cells induced to trilineage differentiation. Gene, 594, 211-219.
- Feldstein AE, Werneburg NW, Canbay A, et al (2004): Free fatty acids promote hepatic lipotoxicity by stimulating TNF‐α expression via a lysosomal pathway. Hepatology, 40, 185-194.
- Geidl-Flueck B, Gerber PA (2017): Insights into the hexose liver metabolism-Glucose versus fructose. Nutrients, 9, 1026.
- Gou SH, Huang HF, Chen XY, et al (2016): Lipid-lowering, hepatoprotective, and atheroprotective effects of the mixture Hong-Qu and gypenosides in hyperlipidemia with NAFLD rats. J Chinese Med Assoc, 79, 111-121.
- Güvenç M, Cellat M, Gökçek İ, et al (2020): Nobiletin attenuates acetaminophen‐induced hepatorenal toxicity in rats. J Biochem Mol Toxicol, 34, e224-227.
- He Z, Jiang T, Wang Z, et al (2004): Modulation of carbohydrate response element-binding protein gene expression in 3T3-L1 adipocytes and rat adipose tissue. Am J Physiol Metab, 287, E424-430.
- Herman MA, Samuel VT (2016): The sweet path to metabolic demise: fructose and lipid synthesis. Trends Endocrinol Metab, 27, 719-730.
- Hirahatake KM, Meissen JK, Fiehn O, et al (2011): Comparative effects of fructose and glucose on lipogenic gene expression and intermediary metabolism in HepG2 liver cells. PLoS One, 6, e26583.
- Janevski M, Ratnayake S, Siljanovski S, et al (2012): Fructose containing sugars modulate mRNA of lipogenic genes ACC and FAS and protein levels of transcription factors ChREBP and SREBP1c with no effect on body weight or liver fat. Food Funct, 3, 141-149.
- Jegatheesan P, Beutheu S, Ventura G, et al (2015); Citrulline and nonessential amino acids prevent fructose-induced nonalcoholic fatty liver disease in rats. J Nutr, 145, 2273-2279.
- Kanuri G, Spruss A, Wagnerberger S, et al (2011): Role of tumor necrosis factor α (TNFα) in the onset of fructose-induced nonalcoholic fatty liver disease in mice. J Nutr Biochem, 22, 527-534.
- Khan HA, Abdelhalim MA, Alhomida AS, et al (2013):Transient increase in IL-1β, IL-6 and TNF-α gene expression in rat liver exposed to gold nanoparticles. Genet Mol Res, 12, 5851-5857.
- Koo HY, Wallig MA, Chung BH, et al (2008): Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liver. Biochim Biophys Acta (BBA)-Molecular Basis Dis, 1782, 341-348.
- Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods, 25, 402–408.
- Lozano I, Van der Werf R, Bietiger W, et al (2016): High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications. Nutr Metab (Lond), 13, 15.
- Luna LG (1968): Manual of histologic staining methods of the Armed Forces Institute of Pathology. McGraw-Hill, New York.
- Matsusue K, Aibara D, Hayafuchi R, et al (2014): Hepatic PPARγ and LXRα independently regulate lipid accumulation in the livers of genetically obese mice. FEBS Lett, 588, 2277-2281.
- Miyazaki M, Dobrzyn A, Man WC, et al (2004): Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and-independent mechanisms. J Biol Chem, 279, 25164-25171.
- Mock K, Lateef S, Benedito VA, et al (2017): High-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulation. J Nutr Biochem, 39, 32-39.
- Mohammadi E, Ghaedi K, Esmailie A, et al (2013): Gene expression profiling of liver X receptor α and Bcl-2-associated X protein in experimental transection spinal cord-injured rats. J Spinal Cord Med, 36, 66-71.
- Ntambi JM, Miyazaki M (2003): Recent insights into stearoyl-CoA desaturase-1. Curr Opin Lipidol, 14, 255-261.
- Ode KL, Frohnert BI, Nathan BM (2009): Identification and treatment of metabolic complications in pediatric obesity. Rev Endocr Metab Disord, 10, 167-188.
- Ouyang X, Cirillo P, Sautin Y, et al (2008): Fructose consumption as a risk factor for non-alcoholic fatty liver disease. J Hepatol, 48, 993-999.
- Ozkan H, Yakan A (2019): Dietary high calories from sunflower oil, sucrose and fructose sources alters lipogenic genes expression levels in liver and skeletal muscle in rats. Ann Hepatol, 18, 15-24.
- Rio DC, Ares M, Hannon GJ, et al (2010): Purification of RNA using TRIzol (TRI reagent). Cold Spring Harb Protoc, 5439.
- Softic S, Cohen DE, Kahn CR (2016): Role of dietary fructose and hepatic de novo lipogenesis in fatty liver disease. Dig Dis Sci, 61, 1282-1293.
- Softic S, Gupta MK, Wang GX, et al (2017): Divergent effects of glucose and fructose on hepatic lipogenesis and insulin signaling. J Clin Invest, 127, 4059-4074.
- Tappy L, Lê KA (2010): Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev, 90, 23-46.
- Vasiljević A, Bursać B, Djordjevic A, et al (2014): Hepatic inflammation induced by high-fructose diet is associated with altered 11βHSD1 expression in the liver of Wistar rats. Eur J Nutr, 53, 1393-1402.
- Yasari S, Prud’homme D, Wang D, et al (2010): Exercise training decreases hepatic SCD-1 gene expression and protein content in rats. Mol Cell Biochem, 335, 291-299.
There are 37 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Veterinary Surgery |
| Journal Section | Research Article |
| Authors | |
| Project Number | 118O381 |
| Publication Date | September 30, 2022 |
| Published in Issue | Year 2022 |