Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Role of obesity and estrogen deficiency in non‑alcoholic fatty liver disease: Insights from a mouse model.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: D. A. Spandidos Country of Publication: Greece NLM ID: 101475259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-3004 (Electronic) Linking ISSN: 17912997 NLM ISO Abbreviation: Mol Med Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: Athens, Greece : D. A. Spandidos
    • Subject Terms:
      Non-alcoholic Fatty Liver Disease*/metabolism ; Non-alcoholic Fatty Liver Disease*/pathology ; Non-alcoholic Fatty Liver Disease*/etiology ; Obesity*/metabolism ; Obesity*/complications ; Obesity*/pathology ; Estrogens*/deficiency; Animals ; Disease Models, Animal ; Male ; Mice ; Female ; Diet, High-Fat/adverse effects ; Liver/pathology ; Liver/metabolism ; Mice, Inbred C57BL ; Insulin Resistance ; Ovariectomy ; Lipid Metabolism ; Menopause
    • Abstract:
      The prevalence of non‑alcoholic fatty liver disease (NAFLD) increases in post‑menopausal women, driven by obesity and metabolic syndrome (MS). However, the pathogenesis of this interaction remains poorly understood. The present study investigated the interplay between obesity, menopause and NAFLD in a C57BL6/J mouse model of diet‑induced obesity. The study included male and female animals, in which a subgroup of females underwent ovariectomy to simulate menopause. Mice were fed a high‑fat diet for 6 months which resulted in them becoming overweight, and developing hyperglycemia and insulin resistance. The present study analyzed liver histology, inflammatory markers and hepatic lipid profiles. All obese animals showed liver steatosis, hepatocyte ballooning and fibrosis. Sex‑related differences were observed, including: i) Obese male mice developed increased expression of inflammatory markers and altered lipid profile; ii) obese female mice exhibited less severe steatosis, hepatic inflammation and lipotoxicity, and iii) ovariectomized obese female mice exhibited exacerbated hepatic lipotoxicity and tissue damage. Ovariectomized obese female mice also had reduced triacylglycerol and cholesteryl ester levels, but increased levels of toxic intermediaries, such as free fatty acids, diacylglycerols and free cholesterol, elevated expression of NF‑κB in the liver and increased levels of serum transaminases, indicating liver damage. These findings suggested that estrogen may protect against NAFLD progression by regulating lipid droplet formation, especially in the context of insulin resistance. More studies in the field are clearly needed to achieve a complete understanding of these pathways, which may serve to improve current therapies.
    • References:
      Metabolism. 2022 Aug;133:155217. (PMID: 35584732)
      Int J Mol Med. 2024 Oct;54(4):. (PMID: 39129305)
      J Diabetes Res. 2015;2015:916585. (PMID: 25883987)
      J Biol Chem. 2002 Nov 8;277(45):42557-62. (PMID: 12200416)
      Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):E8996-E9005. (PMID: 30181290)
      Menopause. 2021 Sep 27;28(11):1296-1306. (PMID: 34581293)
      Climacteric. 2017 Dec;20(6):583-591. (PMID: 29064321)
      Cell Death Dis. 2020 Sep 25;11(9):802. (PMID: 32978374)
      Exp Mol Med. 2017 Feb 3;49(2):e291. (PMID: 28154371)
      J Nutr Sci Vitaminol (Tokyo). 2005 Apr;51(2):110-7. (PMID: 16022198)
      Am J Cardiol. 2017 Nov 15;120(10):1720-1726. (PMID: 28867124)
      Immunol Res. 2011 Aug;50(2-3):113-7. (PMID: 21717079)
      Cell Metab. 2021 Oct 5;33(10):1911-1925. (PMID: 34562355)
      Cell Metab. 2012 Jun 6;15(6):873-84. (PMID: 22682225)
      Nutrition. 2012 Mar;28(3):316-23. (PMID: 22079392)
      Diabetes. 2003 Dec;52(12):2882-7. (PMID: 14633847)
      Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3077-82. (PMID: 12629214)
      Sci Rep. 2023 Sep 19;13(1):15461. (PMID: 37726372)
      Exp Ther Med. 2019 Sep;18(3):1935-1944. (PMID: 31410156)
      Hepatology. 2007 Oct;46(4):1081-90. (PMID: 17654743)
      Hepatology. 2016 Jul;64(1):73-84. (PMID: 26707365)
      Diabetes. 2019 Feb;68(2):291-304. (PMID: 30487265)
      J Clin Invest. 2002 Oct;110(7):905-11. (PMID: 12370266)
      Food Funct. 2019 Sep 1;10(9):6170-6183. (PMID: 31501836)
      Life Sci. 2018 Jun 15;203:291-304. (PMID: 29709653)
      Placenta. 2017 Mar;51:82-88. (PMID: 28292473)
      Hepatol Int. 2021 Feb;15(1):21-35. (PMID: 33548031)
      Prostaglandins Leukot Essent Fatty Acids. 1995 Oct;53(4):239-54. (PMID: 8577777)
      Nutr Metab Cardiovasc Dis. 2011 Feb;21(2):79-85. (PMID: 21186102)
      J Clin Invest. 2006 Nov;116(11):3015-25. (PMID: 17053832)
      Gynecol Endocrinol. 2011 Mar;27(3):156-62. (PMID: 20500105)
      BMC Biol. 2020 Aug 28;18(1):107. (PMID: 32859196)
      Nat Rev Mol Cell Biol. 2019 Mar;20(3):137-155. (PMID: 30523332)
      Cell Metab. 2017 Aug 1;26(2):407-418.e3. (PMID: 28768178)
      Am J Physiol Endocrinol Metab. 2014 May 15;306(10):E1188-97. (PMID: 24691030)
      Sci Rep. 2017 Mar 15;7:44746. (PMID: 28294183)
      Pharmacol Res. 2024 May;203:107155. (PMID: 38527697)
      Int J Mol Sci. 2023 Aug 19;24(16):. (PMID: 37629165)
      Nat Rev Endocrinol. 2023 Aug;19(8):443-459. (PMID: 37221402)
      J Lipid Res. 1983 Apr;24(4):368-80. (PMID: 6854148)
      Arch Intern Med. 2008 Jul 28;168(14):1568-75. (PMID: 18663170)
      Int J Mol Sci. 2023 Jan 05;24(2):. (PMID: 36674549)
      Curr Biol. 2009 Dec 1;19(22):R1046-52. (PMID: 19948145)
      Arterioscler Thromb Vasc Biol. 1998 Mar;18(3):423-31. (PMID: 9514411)
      Endocr J. 2002 Aug;49(4):503-9. (PMID: 12402983)
      Am J Pathol. 2021 Sep;191(9):1490-1498. (PMID: 34102108)
      Trends Cardiovasc Med. 1997 Oct;7(7):256-63. (PMID: 21235894)
      Lipids. 1981 Dec;16(12):920-6. (PMID: 7329212)
      Biochim Biophys Acta. 2014 Dec;1841(12):1648-55. (PMID: 25251292)
      Diabetes. 2013 Feb;62(2):424-34. (PMID: 22966069)
      J Womens Health (Larchmt). 2005 Mar;14(2):137-45. (PMID: 15775731)
      Curr Pharm Des. 2010 Jun;16(17):1941-51. (PMID: 20370677)
      J Hepatol. 2014 Dec;61(6):1376-84. (PMID: 25064435)
      Front Physiol. 2021 Oct 21;12:730829. (PMID: 34744771)
      Balkan Med J. 2023 Feb 01;40(2):93-103. (PMID: 36722753)
      J Br Menopause Soc. 2004 Dec;10(4):157-61. (PMID: 15667752)
      Adv Exp Med Biol. 2017;1043:227-256. (PMID: 29224098)
      Am J Physiol Endocrinol Metab. 2016 Oct 1;311(4):E730-E740. (PMID: 27577854)
      J Dairy Sci. 2021 Nov;104(11):11973-11982. (PMID: 34454753)
      J Hepatol. 2023 Apr;78(4):693-703. (PMID: 36528237)
      J Biol Chem. 1995 Mar 17;270(11):5772-8. (PMID: 7890706)
      Am J Gastroenterol. 2018 Nov;113(11):1649-1659. (PMID: 29880964)
      Am J Physiol Endocrinol Metab. 2009 Jan;296(1):E114-20. (PMID: 18957619)
      J Hepatol. 2012 Jun;56(6):1384-91. (PMID: 22326465)
      Menopause. 2019 Nov;26(11):1327-1333. (PMID: 31567869)
      Endocrinology. 2009 May;150(5):2161-8. (PMID: 19179442)
      Hepatology. 2012 Nov;56(5):1751-9. (PMID: 22707395)
      Prog Lipid Res. 1981;20:41-7. (PMID: 7342101)
      J Biol Chem. 2005 Jun 10;280(23):21763-72. (PMID: 15826936)
      J Endocrinol Invest. 2002 Jun;25(6):547-50. (PMID: 12109627)
      Diabetologia. 2013 May;56(5):949-64. (PMID: 23443243)
    • Contributed Indexing:
      Keywords: Role of obesity and estrogen deficiency in non‑alcoholic fatty liver disease: Insights from a mouse model
    • Accession Number:
      0 (Estrogens)
    • Publication Date:
      Date Created: 20250725 Date Completed: 20250725 Latest Revision: 20250902
    • Publication Date:
      20250902
    • Accession Number:
      PMC12319388
    • Accession Number:
      10.3892/mmr.2025.13629
    • Accession Number:
      40709389