Effect of Combined Action of Triglyceride and Uric Acid on Nonalcoholic Fatty Liver

Yuan Li; Liying Cao

doi:10.54097/jjcksf51

Authors

Yuan Li
Liying Cao

DOI:

https://doi.org/10.54097/jjcksf51

Keywords:

Dyslipidemia, Fatty Liver, Hyperuricemia

Abstract

Objective: To explore whether there is synergistic effect of hyperuric acid and hyperTGemia on the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Methods: In phase one, the hydro-alcoholic extraction of the peel of 750 kg of pomegranate (Punica granatum L.) was performed by the soaking method. Then, in phase two, NAFLD patients received 1500 mg of placebo (n = 37) or pomegranate peel capsules (n = 39) with a 500-kcal deficit diet for 8 weeks. Gastrointestinal intolerance, dietary intake, lipid and glycemic profiles, systolic and diastolic blood pressure, body composition, insulin resistance indexes, and elastography-evaluated NAFLD changes were followed. Results: The mean age of participants was 43.1 ± 8.6 years (51.3% female). Following the intervention, the mean body weight (mean changes: -5.10 ± 2.30 kg), waist circumference (-7.57 ± 2.97 cm), body mass index (-1.82 ± 0.85 kg/m2), body fat index (-1.49 ± 0.86), and trunk fat (- 3.93 ± 3.07%), systolic (-0.63 ± 0.29 cmHg) and diastolic (-0.39 ± 0.19 cmHg) blood pressure, total cholesterol (-10.51 ± 0.77 mg/dl), triglyceride (-16.02 ± 1.7 mg/dl), low-density lipoprotein cholesterol (-9.33 ± 6.66 mg/dl; all P < 0.001), fat free mass (- 0.92 ± 0.90 kg; P < 0.003), and fasting blood sugar (-5.28 ± 1.36 mg/dl; P = 0.02) decreased significantly in PP in contrast to the placebo group in the raw model and when adjusted for confounders. Also, high-density lipoprotein cholesterol (5.10 ± 0.36 mg/dl), liver steatosis and stiffness (- 0.30 ± 0.17 and - 0.72 ± 0.35 kPa, respectively, all P < 0.001) improved in the PP group. However, fasting insulin (P = 0.81) and homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.93) were not significantly different when comparing two groups during the study in the raw and even adjusted models. Conclusion: The interaction between hyperuric acid and hyperTGemia on the onset of NAFLD is synergistic.

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References

[1] Younossi, Z. M. et al Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 64(1), 73–84. https://doi. org/ 10.1002/hep.28431 (2016).

[2] Ge, X., Zheng, L., Wang, M., Du, Y. & Jiang, J. Prevalence trends in non-alcoholic fatty liver disease at the global, regional and national levels, 1990–2017: A population-based observational study. BMJ Open 10(8), e036663. https://doi. org/10.1136/bmjop en-2019-036663 (2020).

[3] Byrne, C. D. & Targher, G. NAFLD: A multisystem disease. J. Hepatol. 62(1 Suppl), S47–S64. https://doi.org/10.1016/ j.jhep.2014.12.012 (2015).

[4] Marchesini, G. et al Nonalcoholic fatty liver, steatohepatitis, and the metabolicsyndrome.Hepatology.37(4),917–923.https:// doi. org/10.1053/jhep.2003.50161 (2003).

[5] Yki-Järvinen, H. Non-alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol.2(11), 901–910. https://doi.org/10.1016/S2213-8587 (14)70032-4 (2014).

[6] Rich, N. E. et al Racial and ethnic disparities in nonalcoholic fatty liver disease prevalence, severity, and outcomes in the United States: A systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 16(2), 198-210.e2. https://doi.org/10. 1016/ j.cgh.2017.09.041 (2018).

[7] Jarvis, Hetal Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies. PLoS Med. 17(4), e1003100. https:// doi. org/10.1371/journal.pmed.1003100 (2020).

[8] Li, Setal Serum uric acid levels and nonalcoholic fatty liver disease: A 2-sample bidirectional mendelian randomization study.J. Clin. Endocrinol. Metab.107(8),e3497–e3503.https:// doi.org/10.1210/clinem/dgac190(2022).

[9] Wei, F.et al Higher serum uric acid level predicts non-alcoholic fatty liver disease: A 4-year prospective cohort study. Front. Endocrinol. (Lausanne). 11, 179. https://doi.org/ 10. 3389/ fendo.2020.00179 (2020).

[10] Sirota, J. C. et al Elevated serum uric acid levels are associated with non-alcoholic fatty liver disease independently of metabolic syndrome features in the United States: Liver ultrasound data from the National Health and Nutrition Examination Survey.Metabolism. 62(3), 392–399. https://doi. org/ 10.1016/j.metabol.2012.08.013 (2013).

[11] Sinha, R. A., Singh, B. K.&Yen, P.M. Direct effects of thyroid hormones on hepatic lipid metabolism. Nat. Rev. Endocrinol. 14 (5), 259–269. https://doi.org/10.1038/nrendo.2018.10 (2018).

[12] Tanase, D. M. et al Hypothyroidism-induced nonalcoholic fatty liver disease (HIN): Mechanisms and emerging therapeutic options. Int. J. Mol. Sci. 21(16), 5927. https://doi.org/ 10.3390/ ijms21165927 (2020).

[13] Hu, Y.et al The nonlinear relationship between thyroid function parameters and metabolic dysfunction-associated fatty liver disease. Front. Endocrinol. (Lausanne). 14,1115354. https:// doi. org/10.3389/fendo.2023.1115354 (2023).

[14] Liu, Y., Wang, W., Yu, X. & Qi, X. Thyroid function and risk of non-alcoholic fatty liver disease in euthyroid subjects. Ann. Hepatol.17(5), 779–788. https://doi.org/10. 5604/01. 3001. 0012. 3136 (2018).

[15] Xu, C., Xu, L., Yu, C., Miao, M. & Li, Y. Association between thyroid function and nonalcoholic fatty liver disease in euthyroid elderly Chinese. Clin. Endocrinol.(Oxf).75(2),240–246. https://doi.org/10.1111/j.1365-2265.2011.04016.x (2011).

[16] Fan, J. G. et al Guidelines for the diagnosis and management of nonalcoholic fatty liver disease: update 2010: (published in Chineseon-Chinese Journal of Hepatology 2010; 18:163–166). J. Dig. Dis. 12(1), 38–44. https://doi.org/10.1111/j.1751-2980. 2010.00476.x (2011).

[17] Alves-Bezerra, M. & Cohen, D. E. Triglyceride metabolism in the liver. Compr. Physiol. 8(1), 1–8. https://doi. org/10. 1002/ cphy.c170012 (2017).

[18] Ji, L., Cai, X., Bai, Y. & Li, T. Application of a novel prediction model for predicting 2-year risk of non-alcoholic fatty liver disease in the non-obese population with normal blood lipid levels: A large prospective cohort study fromChina. Int.J. Gen. Med.14,2909–2922.https:// doi.org/10. 2147/IJGM. S319759 (2021).

[19] März, W. et al HDL cholesterol: Reappraisal of its clinical relevance. Clin.Res.Cardiol.106(9),663–675.https://doi. org/10. 1007/s00392-017-1106-1 (2017).

[20] Cohen, D. E. & Fisher, E. A. Lipoprotein metabolism, dyslipidemia, and nonalcoholic fatty liver disease. Semin. Liver Dis. 33(4), 380–388. https://doi.org/10.1055/s-0033-1358519 (2013).

[21] Verwer, B. J. et al NAFLD is related to post-prandial triglyceride-enrichment of HDL particles in association with endothelial and HDLdysfunction.LiverInt.40(10),2439–2444. https://doi.org/10.1111/liv.14597 (2020).

[22] Deprince, A., Haas, J. T. & Staels, B. Dysregulated lipid metabolism links NAFLD to cardiovascular disease. Mol. Metab. 42, 101092. https://doi.org/ 10.1016/j. molmet. 2020. 101092 (2020).

[23] Feig, D. I., Kang, D. H. & Johnson, R. J. Uric acid and cardiovascular risk.N.Engl.J.Med.359(17),1811–1821. https: // doi. org/10.1056/NEJMra0800885 (2008).

[24] Petta, S., Cammà, C., Cabibi, D., Di Marco, V. & Craxì, A. Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther. 34(7), 757–766. https://doi. org/10.1111/ j. 1365-2036.2011.04788.x (2011).

[25] Xie, D. et al High uric acid induces liver fat accumulation via ROS/JNK/AP-1 signaling. Am. J. Physiol. Endocrinol. Metab. 320 (6), E1032–E1043. https://doi.org/10. 1152/ ajpendo. 00518. 2020 (2021).

[26] Ma, Z. et al Changing trajectories of serum uric acid and risk of non-alcoholic fatty liver disease: A prospective cohort study. J.Transl. Med. 18(1), 133. https://doi.org/10.1186/s12967-020-02296-x (2020).

[27] Cho, Y., Chang, Y., Ryu, S., Wild, S. H. & Byrne, C. D. Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults: The Kangbuk Samsung Health Study. Diabetes Obes. Metab. 26(5), 1644–1657.https:// doi.org/10. 1111/dom.15466 (2024).

[28] Hu, Y. et al High uric acid promotes dysfunction in pancreatic β cells by blocking IRS2/AKT signalling. Mol. Cell Endocrinol. 520, 111070. https://doi.org/10.1016/j.mce.2020.111070 (2021).

[29] Choi, Y. J. et al Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes. Lab.Investig.94(10), 1114–1125. https://doi.org/10.1038/labinvest.2014.98 (2014).

[30] Lai, S., Li, J., Wang, Z., Wang, W. & Guan, H. Sensitivity to thyroid hormone indices are closely associated with NAFLD. Front.Endocrinol.(Lausanne).12,766419.https://doi.org/10.3389/fendo.2021.766419 (2021).

[31] Sinha, R. A. & Yen, P. M. Thyroid hormone-mediated autophagy and mitochondrial turnover in NAFLD.Cell. Biosci. 6,46.https:// doi.org/10.1186/s13578-016-0113-7 (2016).

[32] Bilgin, H. & Pirgon, Ö. Thyroid function in obese children with non-alcoholic fatty liver disease. J. Clin. Res. Pediatr. Endocrinol. 6(3), 152–157. https://doi.org/10.4274/Jcrpe.1488 (2014).

[33] Khan, R. S., Bril, F., Cusi, K. & Newsome, P. N. Modulation of insulin resistance in nonalcoholic fatty liver disease. Hepatology.70(2), 711–724. https://doi.org/ 10.1002/ hep. 30429 (2019).

[34] Cai, X. et al A prediction model based on noninvasive indicators to predict the 8-year incidence of type 2 diabetes in patients with nonalcoholic fatty liver disease: A population-based retrospective cohort study.Biomed.Res. Int.2021, 5527 460. https://doi.org/10.1155/2021/5527460 (2021).

[35] Polyzos, S. A., Kountouras, J. & Mantzoros, C. S. Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics.Metabolism.92,82–97.https:// doi.org/10. 1016/j. metabol. 2018.11.014 (2019).

[36] Hu, J. et al Relationship Between plasma aldosterone concentrations and non-alcoholic fatty liver disease diagnosis in patients with hypertension: A retrospective cohort study. Diabetes. Metab. Syndr. Obes. 16, 1625–1636. https://doi.org/ 10. 2147/DMSO.S408722 (2023).