DOI QR코드

DOI QR Code

Effects of autumn olive berry extract on insulin resistance and non-alcoholic fatty liver in high fructose-fed rat

고과당식이를 급여한 흰쥐에 있어서 토종보리수 추출물의 인슐린 저항성 및 비알콜성 지방간 개선 효과

  • Ha-Neul Choi (Department of Food and Nutrition, Changwon National University) ;
  • Jihye Choi (Health Promotion Department, Korea Association of Health Promotion Gyeongnam Branch) ;
  • Jung-In Kim (Institute of Digital Anti-Aging Healthcare, Inje University)
  • 최하늘 (창원대학교 식품영양학과) ;
  • 최지혜 (한국건강관리협회 경남지부 건강증진과) ;
  • 김정인 (인제대학교 디지털항노화헬스케어학과)
  • Received : 2023.10.29
  • Accepted : 2023.11.29
  • Published : 2023.12.31

Abstract

Purpose: Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the liver which is not a result of excessive alcohol consumption. Its global prevalence was estimated to be approximately 32% in the years 1994-2019. More than half of obese individuals and patients with diabetes are reported to have NAFLD as a comorbidity. This study aimed to investigate the impact of the autumn olive (Elaeagnus umbellata Thunb.) berry on insulin resistance and steatosis in rats fed a high-fructose diet. Methods: Six-week-old Wistar rats were divided into four groups. The control group received a diet consisting of 65% corn starch, while the fructose and experimental groups were fed a diet comprising 65% fructose (FRU) and an FRU diet containing 0.5% (low-dose autumn olive berry group; LAO) or 1.0% (high-dose autumn olive berry group; HAO) ethanol extract of autumn olive berry, respectively, for 10 weeks. Results: The HAO group exhibited significantly lower blood glucose levels compared to the fructose-fed group. Both the LAO and HAO groups showed a substantial reduction in serum insulin levels and insulin resistance when compared to the fructose-fed group. The consumption of LAO and HAO significantly ameliorated dyslipidemia and reduced the levels of triglycerides in the liver compared to the fructose-fed group. Additionally, the consumption of HAO resulted in lower serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to the fructose group. The hepatic expression of the sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) was significantly reduced in the LAO and HAO groups compared to the fructose group. Conclusion: Autumn olive berries improved steatosis by ameliorating insulin resistance and down-regulating the lipogenesis proteins in rats fed on high fructose diet.

토종보리수 열매 추출물의 비알콜성 지방간 질환 개선효과를 규명하기 위해 흰쥐에게 65% 고과당 식이와 함께 토종보리수 열매 에탄올 추출물을 식이의 0.5%, 1.0% 수준으로 10주간 제공하였다. 고과당군은 대조군에 비해 공복 혈당과 혈청 인슐린, HOMA-IR값이 유의적으로 증가하였고, 고농도 보리수 열매 추출물군의 공복혈당은 고과당군에 비해 유의적으로 감소하였다. 저농도 보리수 열매 추출물군 및 고농도 보리수 열매 추출물군의 혈청 인슐린과 HOMA-IR값은 고과당군에 비해 유의적으로 감소하였다. 혈청 중성지방 및 총 콜레스테롤 농도는 고과당군이 대조군에 비해 유의적으로 증가하였으며, 저농도 보리수 열매 추출물군 및 고농도 보리수 열매 추출물군은 고과당군에 비해 유의적으로 감소하였다. 간조직 중성지방 함량은 고과당군이 대조군에 비해 유의적으로 증가하였으며, 저농도 및 고농도 보리수 열매 추출물의 섭취는 고과당군에 비해 유의적으로 감소하였다. 혈청 ALT 및 AST 활성은 고과당군이 대조군에 비해 유의적으로 증가하였고, 저농도 및 고농도 보리수 열매 추출물군의 ALT 활성은 고과당군에 비해 유의적으로 감소하였다. 고농도 보리수 열매 추출군의 AST 활성은 고과당군에 비해 유의적으로 감소하였다. 간조직의 SREBP-1c 및 ChREBP 단백질 발현도는 고과당군이 대조군에 비해 유의적으로 증가하였다. 저농도 및 고농도 보리수 열매 추출물군의 SREBP-1c 및 ChREBP 단백질 발현도는 고과당군에 비해 유의적으로 감소하였고, 대조군과 유의적인 차이가 없었다. 따라서, 고과당을 섭취한 흰쥐에서 토종보리수 열매 추출물의 섭취는 고혈당과 인슐린 저항성 상태를 개선하였고, 혈청 지질과 간조직 중성지방 함량을 감소시켰으며, 간조직의 SREBP-1c 및 ChREBP 단백질 발현을 감소시켜, 비알코올성 지방간질환 개선 효과를 나타내는 것으로 사료된다.

Keywords

Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2016R1D1A3B03930584).

References

  1. Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol 2010; 53(2): 372-384. https://doi.org/10.1016/j.jhep.2010.04.008
  2. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Clin Liver Dis (Hoboken) 2018; 11(4): 81.
  3. Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2022; 7(9): 851-861. https://doi.org/10.1016/S2468-1253(22)00165-0
  4. Im HJ, Ahn YC, Wang JH, Lee MM, Son CG. Systematic review on the prevalence of nonalcoholic fatty liver disease in South Korea. Clin Res Hepatol Gastroenterol 2021; 45(4): 101526.
  5. Negi CK, Babica P, Bajard L, Bienertova-Vasku J, Tarantino G. Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease. Metabolism 2022; 126: 154925.
  6. Pallayova M, Taheri S. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies. Clin Obes 2014; 4(5): 243-253. https://doi.org/10.1111/cob.12068
  7. Dharmalingam M, Yamasandhi PG. Nonalcoholic fatty liver disease and type 2 diabetes mellitus. Indian J Endocrinol Metab 2018; 22(3): 421-428. https://doi.org/10.4103/ijem.IJEM_585_17
  8. Hirano T. Pathophysiology of diabetic dyslipidemia. J Atheroscler Thromb 2018; 25(9): 771-782. https://doi.org/10.5551/jat.RV17023
  9. Tanase DM, Gosav EM, Costea CF, Ciocoiu M, Lacatusu CM, Maranduca MA, et al. The intricate relationship between type 2 diabetes mellitus (T2DM), insulin resistance (IR), and nonalcoholic fatty fiver disease (NAFLD). J Diabetes Res 2020; 2020: 3920196.
  10. Deng KQ, Huang X, Lei F, Zhang XJ, Zhang P, She ZG, et al. Role of hepatic lipid species in the progression of nonalcoholic fatty liver disease. Am J Physiol Cell Physiol 2022; 323(2): C630-C639. https://doi.org/10.1152/ajpcell.00123.2022
  11. Petersen MC, Shulman GI. Roles of diacylglycerols and ceramides in hepatic insulin resistance. Trends Pharmacol Sci 2017; 38(7): 649-665.
  12. Linden AG, Li S, Choi HY, Fang F, Fukasawa M, Uyeda K, et al. Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and lipogenesis in livers of mice. J Lipid Res 2018; 59(3): 475-487. https://doi.org/10.1194/jlr.M081836
  13. Xu X, So JS, Park JG, Lee AH. Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP. Semin Liver Dis 2013; 33(4): 301-311. https://doi.org/10.1055/s-0033-1358523
  14. Matsuzaka T, Shimano H. New perspective on type 2 diabetes, dyslipidemia and non-alcoholic fatty liver disease. J Diabetes Investig 2020; 11(3): 532-534. https://doi.org/10.1111/jdi.13258
  15. Ahmad SD, Sabir SM, Zubair M. Ecotypes diversity in autumn olive (Elaeagnus umbellata Thunb): a single plant with multiple micronutrient genes. Chem Ecol 2006; 22(6): 509-521. https://doi.org/10.1080/02757540601024819
  16. Fordham IM, Clevidence BA, Wiley ER, Zimmerman RH. Fruit of autumn olive: a rich source of lycopene. HortScience 2001; 36(6): 1136-1137. https://doi.org/10.21273/HORTSCI.36.6.1136
  17. Ishaq S, Rathore HA, Sabir SM, Maroof MS. Antioxidant properties of Elaeagnus umbellata berry solvent extracts against lipid peroxidation in mice brain and liver tissues. Food Sci Biotechnol 2015; 24(2): 673-679. https://doi.org/10.1007/s10068-015-0088-x
  18. Khattak KF. Free radical scavenging activity, phytochemical composition and nutrient analysis of Elaeagnus umbellata berry. J Med Plants Res 2012; 6(39): 5196-5203. https://doi.org/10.5897/JMPR11.1128
  19. Zglinska K, Niemiec T, Lozicki A, Matusiewicz M, Szczepaniak J, Puppel K, et al. Effect of Elaeagnus umbellata (Thunb.) fruit extract on H2O2-induced oxidative and inflammatory responses in normal fibroblast cells. PeerJ 2021; 9: e10760.
  20. Kim JI, Baek HJ, Han DW, Yun JA. Autumn olive (Elaeagnus umbellata Thunb.) berry reduces fasting and postprandial glucose levels in mice. Nutr Res Pract 2019; 13(1): 11-16. https://doi.org/10.4162/nrp.2019.13.1.11
  21. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28(7): 412-419. https://doi.org/10.1007/BF00280883
  22. 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; 226(1): 497-509.  https://doi.org/10.1016/S0021-9258(18)64849-5
  23. Teff KL, Grudziak J, Townsend RR, Dunn TN, Grant RW, Adams SH, et al. Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: influence of insulin resistance on plasma triglyceride responses. J Clin Endocrinol Metab 2009; 94(5): 1562-1569. https://doi.org/10.1210/jc.2008-2192
  24. Reddy SS, Ramatholisamma P, Karuna R, Saralakumari D. Preventive effect of Tinospora cordifolia against high-fructose diet-induced insulin resistance and oxidative stress in male Wistar rats. Food Chem Toxicol 2009; 47(9): 2224-2229. https://doi.org/10.1016/j.fct.2009.06.008
  25. Mohamed MA, Ahmed MA, Abd Elbast SA, Ali NA. Rice bran oil ameliorates hepatic insulin resistance by improving insulin signaling in fructose fed-rats. J Diabetes Metab Disord 2019; 18(1): 89-97. https://doi.org/10.1007/s40200-019-00394-2
  26. Dziadek K, Kopec A, Piatkowska E, Leszczynska T. High-fructose diet-induced metabolic disorders were counteracted by the intake of fruit and leaves of sweet cherry in Wistar rats. Nutrients 2019; 11(11): 2638.
  27. Viskelis P, Rubinskiene M, Jasutiene I, Sarkinas A, Daubaras R, Cesoniene L. Anthocyanins, antioxidative, and antimicrobial properties of American cranberry (Vaccinium macrocarpon Ait.) and their press cakes. J Food Sci 2009; 74(2): C157-C161. https://doi.org/10.1111/j.1750-3841.2009.01066.x
  28. Rodrigues CA, Nicacio AE, Boeing JS, Garcia FP, Nakamura CV, Visentainer JV, et al. Rapid extraction method followed by a d-SPE clean-up step for determination of phenolic composition and antioxidant and antiproliferative activities from berry fruits. Food Chem 2020; 309: 125694.
  29. Williamson G, Sheedy K. Effects of polyphenols on insulin resistance. Nutrients 2020; 12(10): 3135.
  30. Hassan NF, Hassan AH, El-Ansary MR. Cytokine modulation by etanercept ameliorates metabolic syndrome and its related complications induced in rats administered a high-fat high-fructose diet. Sci Rep 2022; 12(1): 20227.
  31. Jiang L, Yao L, Yang Y, Ke D, Batey R, Wang J, et al. Jiangzhi Capsule improves fructose-induced insulin resistance in rats: association with repair of the impaired sarcolemmal glucose transporter-4 recycling. J Ethnopharmacol 2016; 194: 288-298. https://doi.org/10.1016/j.jep.2016.09.009
  32. Ichigo Y, Takeshita A, Hibino M, Nakagawa T, Hayakawa T, Patel D, et al. High-fructose diet-induced hypertriglyceridemia is associated with enhanced hepatic expression of ACAT2 in rats. Physiol Res 2019; 68(6): 1021-1026. https://doi.org/10.33549/physiolres.934226
  33. Wong VW, Wong GL, Yeung JC, Fung CY, Chan JK, Chang ZH, et al. Long-term clinical outcomes after fatty liver screening in patients undergoing coronary angiogram: a prospective cohort study. Hepatology 2016; 63(3): 754-763. https://doi.org/10.1002/hep.28253
  34. Nazir N, Zahoor M, Nisar M, Khan I, Karim N, Abdel-Halim H, et al. Phytochemical analysis and antidiabetic potential of Elaeagnus umbellata (Thunb.) in streptozotocin-induced diabetic rats: pharmacological and computational approach. BMC Complement Altern Med 2018; 18(1): 332.
  35. Sattar N, Forrest E, Preiss D. Non-alcoholic fatty liver disease. BMJ 2014; 349: g4596.
  36. Kim J, Nam KS, Noh SK. Cherry silverberry (Elaeagnus multiflora) wine mitigates the development of alcoholic fatty liver in rats. J Korean Soc Food Sci Nutr 2012; 41(1): 57-64.  https://doi.org/10.3746/jkfn.2012.41.1.057
  37. Iftikhar N, Hussain AI, Chatha SA, Sultana N, Rathore HA. Effects of polyphenol-rich traditional herbal teas on obesity and oxidative stress in rats fed a high-fat-sugar diet. Food Sci Nutr 2022; 10(3): 698-711. https://doi.org/10.1002/fsn3.2695
  38. Li W, Yang H, Zhao Q, Wang X, Zhang J, Zhao X. Polyphenol-rich loquat fruit extract prevents fructose-induced nonalcoholic fatty liver disease by modulating glycometabolism, lipometabolism, oxidative stress, inflammation, intestinal barrier, and gut microbiota in mice. J Agric Food Chem 2019; 67(27): 7726-7737.  https://doi.org/10.1021/acs.jafc.9b02523
  39. Miyazaki M, Dobrzyn A, Man WC, Chu K, Sampath H, Kim HJ, et al. 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 2004; 279(24): 25164-25171. https://doi.org/10.1074/jbc.M402781200
  40. Fenni S, Hammou H, Astier J, Bonnet L, Karkeni E, Couturier C, et al. Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders. Mol Nutr Food Res 2017; 61(9): 1601083.
  41. Mannino F, Pallio G, Altavilla D, Squadrito F, Vermiglio G, Bitto A, et al. Atherosclerosis plaque reduction by lycopene is mediated by increased energy expenditure through AMPK and PPARα in ApoE KO mice fed with a high fat diet. Biomolecules 2022; 12(7): 973.