BMI trajectories are associated with NAFLD and advanced fibrosis via aging-inflammation mediation.

Publisher: BioMed Central Country of Publication: England NLM ID: 100968562 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2458 (Electronic) Linking ISSN: 14712458 NLM ISO Abbreviation: BMC Public Health Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Non-alcoholic Fatty Liver Disease*/epidemiology ; Body Mass Index* ; Inflammation* ; Aging*/physiology ; Liver Cirrhosis*/epidemiology; Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; Nutrition Surveys ; Obesity/epidemiology ; Disease Progression

Background: As the global epidemic of obesity fuels metabolic conditions, the burden of nonalcoholic fatty liver disease (NAFLD) will become enormous. Abundant studies revealed the association between high body mass index (BMI) and NAFLD but overlooked the BMI patterns across life stages. We aimed to explore how BMI trajectories over age relate to NAFLD.
Methods: Selecting 3212 participants in NHANES 2017-2020, we tracked BMI records at different ages. Using a latent class trajectory model (LCTM), we identified BMI trajectories over age. Multinomial logistic regression assessed their association with NAFLD and advanced fibrosis. Structural equation modeling (SEM) revealed mediation effects.
Results: We identified 3 BMI trajectories: Steady Progression, Increase to Decrease, and Rapid Ascending. There was no significant difference in NAFLD/advanced fibrosis risk between the increase-to-decrease group and the steady progression group. The Rapid Ascending trajectory significantly correlated with NAFLD (OR = 2.21, 95% CI 1.29-3.77) and advanced fibrosis (OR = 3.04, 95% CI 1.13-8.22). This association was influenced by a chain-mediated process of phenotypic age and C-reactive protein (mediated effect to NAFLD = 0.010, p < 0.01; mediated effect to advanced fibrosis = 0.003, p < 0.05). This mediation on NAFLD was independent of insulin resistance (IR). The association between rapid ascending trajectory and advanced fibrosis was more pronounced among the male subgroup (p for interaction = 0.008).
Conclusion: The rapid ascending trajectory of BMI correlates with an increased susceptibility to NAFLD and advanced fibrosis independent of BMI, mediated by aging and inflammation. Our results suggest that long-term maintenance of BMI is pivotal in NAFLD prevention. Aging-inflammation may represent a distinct mechanism of sustained obesity to NAFLD, independent of IR.
Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2025. The Author(s).)

Medicine (Baltimore). 2015 Dec;94(48):e2159. (PMID: 26632897)
JAMA. 2020 Mar 24;323(12):1175-1183. (PMID: 32207804)
Pain Med. 2020 Mar 1;21(3):439-447. (PMID: 31386156)
Front Endocrinol (Lausanne). 2019 Feb 26;10:114. (PMID: 30863366)
Front Endocrinol (Lausanne). 2022 Feb 17;13:820932. (PMID: 35250879)
Nat Commun. 2022 Jan 31;13(1):578. (PMID: 35102146)
Semin Cancer Biol. 2023 Jul;92:16-27. (PMID: 36965839)
Lancet Psychiatry. 2016 Jul;3(7):628-35. (PMID: 27138970)
Hepatology. 2023 May 1;77(5):1797-1835. (PMID: 36727674)
Lancet Gastroenterol Hepatol. 2022 Sep;7(9):851-861. (PMID: 35798021)
Gastroenterology. 2020 May;158(7):1899-1912. (PMID: 32061598)
Aging (Albany NY). 2018 Apr 18;10(4):573-591. (PMID: 29676998)
Nat Rev Gastroenterol Hepatol. 2021 Apr;18(4):223-238. (PMID: 33349658)
Aliment Pharmacol Ther. 2023 May;57(10):1143-1150. (PMID: 36924053)
J Hepatol. 2023 Aug;79(2):516-537. (PMID: 36990226)
Clin Gastroenterol Hepatol. 2023 Jul;21(8):1978-1991. (PMID: 37121527)
J Clin Invest. 2019 Oct 1;129(10):3990-4000. (PMID: 31573548)
Vital Health Stat 1. 2022 May;(190):1-36. (PMID: 35593699)
JAMA. 2019 Feb 12;321(6):602-603. (PMID: 30676631)
Cell Immunol. 2018 Oct;332:111-120. (PMID: 30103942)
J Clin Invest. 2020 Mar 2;130(3):1453-1460. (PMID: 31805015)
Minerva Endocrinol. 2017 Jun;42(2):92-108. (PMID: 27711029)
Semin Cell Dev Biol. 2020 Dec;108:72-81. (PMID: 32444289)
Inflammation. 2017 Dec;40(6):1875-1883. (PMID: 28730512)
Ann Intern Med. 2017 Aug 15;167(4):268-274. (PMID: 28693043)
J Hepatol. 2014 Sep;61(3):626-32. (PMID: 24768828)
BMJ. 2017 Nov 14;359:j4849. (PMID: 29138133)
Lancet. 2021 Jun 5;397(10290):2212-2224. (PMID: 33894145)
Gut. 2022 May;71(5):1006-1019. (PMID: 34001645)
Int J Environ Res Public Health. 2020 Apr 11;17(8):. (PMID: 32290381)
Cell Death Dis. 2022 Apr 4;13(4):300. (PMID: 35379822)
Clin Rev Allergy Immunol. 2023 Apr;64(2):109-122. (PMID: 34536213)
Liver Int. 2018 Apr;38(4):706-714. (PMID: 28963767)
Endocr Pract. 2022 May;28(5):528-562. (PMID: 35569886)

Keywords: Advanced fibrosis; Aging; BMI trajectory; Inflammation; NAFLD

Date Created: 20250113 Date Completed: 20250114 Latest Revision: 20250206

20250206

PMC11730164

10.1186/s12889-025-21322-5

39806323