5-Lipooxygenase Derivatives as Serum Biomarkers of a Successful Dietary Intervention in Patients with NonAlcoholic Fatty Liver Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Anthropometric Measurements, Body Mass Reduction
2.3. The Fatty Liver Index ( FLI)
2.4. Dietary Intervention
2.5. Fatty Acid Derivatives Measurement
2.6. Statistical Analysis
3. Results
3.1. Changes in the Anthropometric and Biochemical Parameters in Both Groups
3.2. Changes in the Fatty Acid Derivatives
3.3. The Concentration of the Lipid Derivatives Correlated With the Parameters of Liver Steatosis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Cano, A.; Alonso, C. Deciphering nonalcoholic fatty liver disease through metabolomics. Biochem. Soc. Trans. 2014, 42, 1447–1452. [Google Scholar] [CrossRef]
- Marino, L.; Jornayvaz, F.R. Endocrine causes of nonalcoholic fatty liver disease. World J. Gastroenterol. 2015, 21, 11053–11076. [Google Scholar] [CrossRef]
- Lonardo, A.; Bellentani, S.; Argo, C.K.; Ballestri, S.; Byrne, C.D.; Caldwell, S.H.; Cortez-Pinto, H.; Grieco, A.; Machado, M.V.; Miele, L.; et al. Epidemiological modifiers of nonalcoholic fatty liver disease: Focus on high-risk groups. Dig. Liver Dis. 2015, 47, 997–1006. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Milic, S.; Lulic, D.; Stimac, D. Nonalcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations. World J. Gastroenterol. 2014, 20, 9330–9397. [Google Scholar] [PubMed]
- Brea, A.; Puzo, J. Nonalcoholic fatty liver disease and cardiovascular risk. Int. J. Cardiol. 2013, 167, 1109–1117. [Google Scholar] [CrossRef] [PubMed]
- Pallayova, M.; Taheri, S. Nonalcoholic fatty liver disease in obese adults: Clinical aspects and current management strategies. Clin. Obes. 2014, 4, 243–253. [Google Scholar] [CrossRef]
- Ferreira, V.S.; Pernambuco, R.B.; Lopes, E.P.; Morais, C.N.; Rodrigues, M.C.; Arruda, M.J.; Vilar, L. Frequency and risk factors associated with nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Arquivos Brasileiros De Endocrinologia E Metabologia 2010, 54, 362–368. [Google Scholar] [CrossRef] [Green Version]
- Puri, P.; Baillie, R.A.; Wiest, M.M.; Mirshahi, F.; Choudhury, J.; Cheung, O.; Sargeant, C.; Contos, M.J.; Sanyal, A.J. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology 2007, 46, 1081–1090. [Google Scholar] [CrossRef]
- Volpe, C.M.; Nogueira-Machado, J.A. The dual role of free fatty acid signaling ininflammation and therapeutics. Recent Pat. Endocr. Metab. Immune Drug Discov. 2013, 7, 189–197. [Google Scholar] [CrossRef]
- Feldstein, A.E.; Lopez, R.; Tamimi, T.A.; Yerian, L.; Chung, Y.M.; Berk, M.; Zhang, R.; McIntyre, T.M.; Hazen, S.L. Mass spectrometric profiling of oxidized products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J. Lipid Res. 2010, 51, 3046–3054. [Google Scholar] [CrossRef] [Green Version]
- Pickens, C.A.; Sordillo, L.M.; Zhang, C.; Fenton, J.I. Obesity is positively associated with arachidonic acid-derived 5- and 11-hydroxyeicosatetraenoic acid (HETE). Metabolism 2017, 70, 177–191. [Google Scholar] [CrossRef]
- Powell, W.S.; Rokach, J. Biosynthesis. biological effects. and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid. Biochimica Et Biophys. Acta Mol. Cell Biol. Lipids 2015, 1851, 340–355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mashima, R.; Okuyama, T. The role of lipoxygenases in pathophysiology; new insights and future perspectives. Redox Biol. 2015, 6, 297–310. [Google Scholar] [CrossRef] [Green Version]
- Sobrado, M.; Pereira, M.P.; Ballesteros, I.; Hurtado, O.; Fernandez-Lopez, D.; Pradillo, J.M.; Caso, J.R.; Vivancos, J.; Nombela, F.; Serena, J.; et al. Synthesis of Lipoxin A(4) by 5-Lipoxygenase Mediates PPAR gamma-Dependent. Neuroprotective Effects of Rosiglitazone in Experimental Stroke. J. Neurosci. 2009, 29, 3875–3884. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maciejewska, D.; Ossowski, P.; Drozd, A.; Ryterska, K.; Jamioł-Milc, D.; Banaszczak, M.; Kaczorowska, M.; Sabinicz, A.; Raszeja-Wyszomirska, J.; Stachowska, E. Metabolites of arachidonic acid and linoleic acid in early stages of nonalcoholic fatty liver disease-A pilot study. Prostaglandins Other Lipid Mediat. 2015, 121, 184–189. [Google Scholar] [CrossRef] [PubMed]
- Stachowska, E.; Maciejewska, D.; Ossowski, P.; Drozd, A.; Ryterska, K.; Banaszczak, M.; Milkiewicz, M.; Raszeja-Wyszomirska, J.; Slebioda, M.; Milkiewicz, P.; et al. Apolipoprotein E4 allele is associated with substantial changes in the plasma lipids and hyaluronic acid content in patients with nonalcoholic fatty liver disease. J. Physiol. Pharmacol. 2013, 64, 711–717. [Google Scholar] [PubMed]
- Selezneva, K.S.; Isakov, V.A.; Éller, K.I.; Goriainov, S.V.; Kirillova, O.O.; Sentsova, T.B. Isomeric specific analysis of hydroxyeicosatetraenoic acid in blood samples from obese patients with nonalcoholic and alcoholic steatohepatitis. Vopr. Pitan. 2014, 83, 12–19. [Google Scholar]
- Möller, K.; Ostermann, A.I.; Rund, K.; Thoms, S.; Blume, C.; Stahl, F.; Hahn, A.; Schebb, N.H.; Schuchardt, J.P. Influence of weight reduction on blood levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and oxylipins in obese subjects. Prostaglandins Leukot. Essent Fat. Acids 2016, 106, 39–49. [Google Scholar] [CrossRef]
- Jiang, X.Q.; Li, Z.H.; Jiang, S.F.; Tong, X.F.; Zou, X.J.; Wang, W.; Zhang, W.Z.; Wu, L. Lipoxin A4 exerts protective effects against experimental acute liver failure by inhibiting the NF-kappa B pathway. Int. J. Mol. Med. 2016, 37, 773–780. [Google Scholar] [CrossRef] [Green Version]
- Tsao, C.C.; Foley, J.; Coulter, S.J.; Maronpot, R.; Zeldin, D.C.; Goldstein, J.A. CYP2C40, a unique arachidonic acid 16-hydroxylase, is the major CYP2C in murine intestinal tract. Mol. Pharmacol. 2000, 58, 279–287. [Google Scholar] [CrossRef] [Green Version]
- Kammerer, I.; Ringseis, R.; Biemann, R.; Wen, G.P.; Eder, K. 13-hydroxy linoleic acid increases expression of the cholesterol transporters ABCA1, ABCG1 and SR-BI and stimulates apoA-I-dependent cholesterol efflux in RAW264.7 macrophages. Lipids Health Dis. 2011, 10, 222. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Horrillo, R.; González-Périz, A.; Martínez-Clemente, M.; López-Parra, M.; Ferré, N.; Titos, E.; Morán-Salvador, E.; Deulofeu, R.; Arroyo, V.; Clària, J. 5-Lipoxygenase activating protein signals adipose tissue inflammation and lipid dysfunction inexperimental obesity. J. Immunol. 2010, 184, 3978–3987. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Weaver, J.R.; Holman, T.R.; Imai, Y.; Jadhav, A.; Kenyon, V.; Maloney, D.J.; Nadler, J.L.; Rai, G.; Simeonov, D.A.; Taylor-Fishwick, D.A. Integration of pro-inflammatory cytokines, 12-lipoxygenase and NOX-1 in pancreatic islet beta cell dysfunction. Mol. Cell. Endocrinol. 2012, 358, 88–95. [Google Scholar] [CrossRef] [PubMed]
- Wang, N.N.; Zhao, X.N.; Wang, W.H.; Peng, Y.; Bi, K.S.; Dai, R.H. Targeted profiling of arachidonic acid and eicosanoids in rat tissue by UFLC-MS/MS: Application to identify potential markers for rheumatoid arthritis. Talanta 2017, 162, 479–487. [Google Scholar] [CrossRef] [PubMed]
- Muro, S.; Hamid, Q.; Olivenstein, R.; Taha, R.; Rokach, J.; Powell, W.S. 5-Oxo-6,8,11,14-eicosatetraenoic acid induces the infiltration of granulocytes into human skin. J. Allergy Clin. Immunol. 2003, 112, 768–774. [Google Scholar] [CrossRef]
- Stachowska, E.; Ryterska, K.; Maciejewska, D.; Banaszczak, M.; Milkiewicz, P.; Milkiewicz, M.; Gutowska, I.; Ossowski, P.; Kaczorowska, M.; Jamioł-Milc, D.; et al. Nutritional Strategies for the Individualized Treatment of NonAlcoholic Fatty Liver Disease (NAFLD) Based on the Nutrient-Induced Insulin Output Ratio (NIOR). Int. J. Mol. Sci. 2016, 17, 1192. [Google Scholar] [CrossRef] [Green Version]
- Hamaguchi, M.; Kojima, T.; Itoh, Y.; Harano, Y.; Fujii, K.; Nakajima, T.; Kato, T.; Takeda, N.; Okuda, J.; Ida, K.; et al. The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation. Am. J. Gastroenterol. 2007, 102, 2708–2715. [Google Scholar] [CrossRef]
- Copyright 1997–2020 by Geoffrey C Urbaniak and Scott Plous. Available online: https://www.randomizer.org/ (accessed on 3 February 2020).
- Bedogni, G.; Bellentani, S.; Miglioli, L.; Masutti, F.; Passalacqua, M.; Castiglione, A.; Tiribelli, C. The Fatty Liver Index: A simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol. 2006, 6, 1–7. [Google Scholar] [CrossRef] [Green Version]
- Musso, G.; Cassader, M.; Rosina, F.; Gambino, R. Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in nonalcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of randomised trials. Diabetologia 2012, 55, 885–904. [Google Scholar] [CrossRef]
- Chalasani, N.; Younossi, Z.; Lavine, J.E.; Charlton, M.; Cusi, K.; Rinella, M.; Harrison, S.A.; Brunt, E.M.; Sanyal, A.J. The diagnosis and management of nonalcoholic fatty liver disease Practice guidance from the American association for Study of liver diseases. Hepatology 2018, 67, 2478–2479. [Google Scholar] [CrossRef] [Green Version]
- Puri, P.; Wiest, M.M.; Cheung, O.; Mirshahi, F.; Sargeant, C.; Min, H.K.; Contos, M.J.; Sterling, R.K.; Fuchs, M.; Zhou, H.; et al. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology 2009, 50, 1827–1838. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Raszeja-Wyszomirska, J.; Safranow, K.; Milkiewicz, M.; Milkiewicz, P.; Szynkowska, A.; Stachowska, E. Lipidic last breath of life in patients with alcoholic liver disease. Prostaglandins Other Lipid Mediat. 2012, 99, 51–56. [Google Scholar] [CrossRef]
- Dandona, P.; Mohanty, P.; Ghanim, H.; Aljada, A.; Browne, R.; Hamouda, W.; Prabhala, A.; Afzal, A.; Garg, R. The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation. J. Clin. Endocrinol. Metab. 2001, 86, 355–362. [Google Scholar] [PubMed] [Green Version]
- Soumya, S.J.; Binu, S.; Helen, A.; Reddanna, P.; Sudhakaran, P.R. 15(S)-HETE-induced angiogenesis in adipose tissue is mediated through activation of PI3K/Akt/mTOR signaling pathway. Biochem. Cell Biol. 2013, 91, 498–505. [Google Scholar] [CrossRef] [PubMed]
- Song, Y.S.; Lee, D.H.; Yu, J.H.; Oh, D.K.; Hong, J.T.; Yoon, D.Y. Promotion of adipogenesis by 15-(S)-hydroxyeicosatetraenoic acid. Prostaglandins Other Lipid Mediat. 2016, 123, 1–8. [Google Scholar] [CrossRef]
- Dobrian, A.D.; Huyck, R.W.; Glenn, L.; Gottipati, V.; Haynes, B.A.; Hansson, G.I.; Marley, A.; McPheat, W.L.; Nadler, J.L. Activation of the 12/15 lipoxygenase pathway accompanies metabolic decline in db/db pre-diabetic mice. Prostaglandins Other Lipid Mediat. 2018, 136, 23–32. [Google Scholar] [CrossRef]
- Lieb, D.C.; Brotman, J.J.; Hatcher, M.A.; Aye, M.S.; Cole, B.K.; Haynes, B.A.; Wohlgemuth, S.D.; Fontana, M.A.; Beydoun, H.; Nadle, J.L.; et al. Adipose tissue 12/15 lipoxygenase pathway in human obesity and diabetes. J. Clin. Endocrinol. Metab. 2014, 99, E1713–E1720. [Google Scholar] [CrossRef] [Green Version]
- Cossette, C.; Gravel, S.; Reddy, C.N.; Gore, V.; Chourey, S.; Ye, Q.J.; Snyder, N.W.; Mesaros, C.A.; Blair, J.A.; Lavoie, J.P.; et al. Biosynthesis and actions of 5-oxoeicosatetraenoic acid (5-oxo-ETE) on feline granulocytes. Biochem. Pharmacol. 2015, 96, 247–255. [Google Scholar] [CrossRef] [Green Version]
- Martínez-Clemente, M.; Clària, J.; Titos, E. The 5-lipoxygenase/leukotriene pathway in obesity, insulin resistance, and fatty liver disease. Curr. Opin. Clin. Nutr. Metab. Care 2011, 14, 347–353. [Google Scholar] [CrossRef]
Product | Function in the Organism | Research Model | Source |
---|---|---|---|
A4 Lipoxins | It affects the reduction of tumor necrosis factor (TNF)-α and Interleukin (IL)-6 in plasma. Decreases liver cell apoptosis. | Mice | [19] |
16(S)-HETE | The inhibition of the adhesion and aggregation of neutrophils in the intestines. | Mice, human | [20] |
9 13(S)-HODE | A strong correlation with liver histopathology (inflammation, fibrosis and steatosis). An activator of Low density lipoprotein (LDL) oxidation. It affects the increase in the secretion of cholesterol from macrophages. | Mice, human cell line | [10] [21] |
5(S)-HETE | The sensitisation of hepatocytes towards apoptosis induced by TNF-α 5. A prominent role in the inflammatory process. Activation of hepatic stellate cells and Nonalcoholic fatty liver disease (NAFLD) progression. | Human cell line, murine | [22] |
12(S)-HETE | The stimulation of the expression of Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase on pancreatic islets. The induction of inflammation via the stimulation of protein kinase C. | Cell line Rats | [23] [24] |
15(S)-HETE | An inflammation marker. | Rats | [24] |
5-oxo ETE | Strong eosinophils’ activator acting as a chemoattractant | Humans | [25] |
Δ (t0-t1 ) | Group I n = 52 | Group II n = 16 | p |
---|---|---|---|
Δ Body mass index (BMI) (kg/m2) | −2.30 ± 1.54 | −1.38 ± 1.42 | 0.04 |
Δ Waist circumference (cm) | −8.28 ± 13.5 | −3.09 ± 5.43 | 0.03 |
Δ Stage of steatosis(Hamaguchi score) | −1.44 ± 0.64 | 0.00 | <0.0001 |
Δ Fatty Liver Index (FLI) | −12.38 ± 13.83 | −6 ± 8.48 | 0.035 |
Δ AST (U/L) | −4.11± 11.69 | 1.87 ± 13.54 | 0.01 |
Δ ALT (U/L) | −10.65 ± 29.23 | −19.12 ± 32.54 | 0.70 |
Δ GGTP (U/L) | −16.94 ± 51.16 | 13.62 ± 81.78 | 0.25 |
Δ Triglycerides (mg/dL) | −20.19 ± 93.36 | 45.37 ± 80.66 | 0.001 |
Δ Cholesterol (mg/dL) | −9.46 ± 33.49 | 21.00 ± 31.57 | 0.004 |
Δ High-density lipoproteins (HDL) (mg/dL) | 2.65 ± 7.55 | 2.56 ± 5.27 | 0.94 |
Δ Low-density lipoproteins (mg/dL) | −3.19± 43.50 | 11.06 ± 29.05 | 0.15 |
Δ Glucose (mg/dL) | −0.15 ± 12.35 | 6.06 ± 17.29 | 0.21 |
Δ Insulin (U/mL) | −3.77 ± 10.47 | −4.42 ± 7.46 | 0.70 |
Eicosanoids μg/mL | Group I, n = 52 Δ t0–t1 Median (IQR) | Group II, n = 16 Δ t0–t1 Median (IQR ) | p |
---|---|---|---|
LTX A4 | −0.09 (1.17) | 0.52 (1.02) | 0.02 |
16(S)-HETE | −0.03 (0.35) | 0.05 (0.46) | 0.45 |
13(S)-HODE | −0.56 (3.17) | −0.05 (4.35) | 0.43 |
9(S)-HODE | −1.00 (3.72) | −0.16 (5.40) | 0.45 |
15(S)-HETE | −0.93 (7.09) | 0.58 (11.28) | 0.96 |
12(S)-HETE | 1.52 (10.38) | 2.16 (10.86) | 0.83 |
5-oxo–ETE | −0.01 (1.24) | 0.73 (1.80) | 0.01 |
NAFLD Parameters | Eicosanoids | Rho | p |
---|---|---|---|
Stage of liver steatosis | 5-S HETE | 0.28 | p < 0.05 |
5-oxo-ETE | 0.29 | p < 0.05 | |
ALT | 5-S-HETE | 0.29 | p < 0.05 |
5-oxo-ETE | 0.32 | p < 0.05 | |
HOMA-IR | 5-S HETE | 0.30 | p < 0.05 |
Fatty Liver Index | - | - | - |
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Banaszczak, M.; Maciejewska, D.; Drozd, A.; Ryterska, K.; Milc, D.J.; Raszeja-Wyszomirska, J.; Wunsch, E.; González-Muniesa, P.; Stachowska, E. 5-Lipooxygenase Derivatives as Serum Biomarkers of a Successful Dietary Intervention in Patients with NonAlcoholic Fatty Liver Disease. Medicina 2020, 56, 58. https://doi.org/10.3390/medicina56020058
Banaszczak M, Maciejewska D, Drozd A, Ryterska K, Milc DJ, Raszeja-Wyszomirska J, Wunsch E, González-Muniesa P, Stachowska E. 5-Lipooxygenase Derivatives as Serum Biomarkers of a Successful Dietary Intervention in Patients with NonAlcoholic Fatty Liver Disease. Medicina. 2020; 56(2):58. https://doi.org/10.3390/medicina56020058
Chicago/Turabian StyleBanaszczak, Marcin, Dominika Maciejewska, Arleta Drozd, Karina Ryterska, Dominika Jamioł Milc, Joanna Raszeja-Wyszomirska, Ewa Wunsch, Pedro González-Muniesa, and Ewa Stachowska. 2020. "5-Lipooxygenase Derivatives as Serum Biomarkers of a Successful Dietary Intervention in Patients with NonAlcoholic Fatty Liver Disease" Medicina 56, no. 2: 58. https://doi.org/10.3390/medicina56020058