Effects of maternal diet-induced obesity on metabolic disorders and age-associated miRNA expression in the liver of male mouse offspring.
Authors
Mennitti, Laís Vales
Carpenter, Asha AM
Loche, Elena
Pantaleão, Lucas C
Blackmore, Heather L
Ashmore, Thomas J
Pisani, Luciana Pellegrini
Hargreaves, Iain
Publication Date
2022-02Journal Title
Int J Obes (Lond)
ISSN
0307-0565
Publisher
Springer Science and Business Media LLC
Volume
46
Issue
2
Pages
269-278
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Mennitti, L. V., Carpenter, A. A., Loche, E., Pantaleão, L. C., Fernandez-Twinn, D. S., Schoonejans, J. M., Blackmore, H. L., et al. (2022). Effects of maternal diet-induced obesity on metabolic disorders and age-associated miRNA expression in the liver of male mouse offspring.. Int J Obes (Lond), 46 (2), 269-278. https://doi.org/10.1038/s41366-021-00985-1
Abstract
OBJECTIVE: This study investigated the effect of maternal obesity on aged-male offspring liver phenotype and hepatic expression of a programmed miRNA. METHODS: A mouse model (C57BL/6 J) of maternal diet-induced obesity was used to investigate fasting-serum metabolites, hepatic lipid content, steatosis, and relative mRNA levels (RT-PCR) and protein expression (Western blotting) of key components involved in hepatic and mitochondrial metabolism in 12-month-old offspring. We also measured hepatic lipid peroxidation, mitochondrial content, fibrosis stage, and apoptosis in the offspring. To investigate potential mechanisms leading to the observed phenotype, we also measured the expression of miR-582 (a miRNA previously implicated in liver cirrhosis) in 8-week-old and 12-month-old offspring. RESULTS: Body weight and composition was similar between 8-week-old offspring, however, 12-month-old offspring from obese mothers had increased body weight and fat mass (19.5 ± 0.8 g versus 10.4 ± 0.9 g, p < 0.001), as well as elevated serum levels of LDL and leptin and hepatic lipid content (21.4 ± 2.1 g versus 12.9 ± 1.8 g, p < 0.01). This was accompanied by steatosis, increased Bax/Bcl-2 ratio, and overexpression of p-SAPK/JNK, Tgfβ1, Map3k14, and Col1a1 in the liver. Decreased levels of Bcl-2, p-AMPKα, total AMPKα and mitochondrial complexes were also observed. Maternal obesity was associated with increased hepatic miR-582-3p (p < 0.001) and miR-582-5p (p < 0.05). Age was also associated with an increase in both miR-582-3p and miR-582-5p, however, this was more pronounced in the offspring of obese dams, such that differences were greater in 12-month-old animals (-3p: 7.34 ± 1.35 versus 1.39 ± 0.50, p < 0.0001 and -5p: 4.66 ± 1.16 versus 1.63 ± 0.65, p < 0.05). CONCLUSION: Our findings demonstrate that maternal diet-induced obesity has detrimental effects on offspring body composition as well as hepatic phenotype that may be indicative of accelerated-ageing phenotype. These whole-body and cellular phenotypes were associated with age-dependent changes in expression of miRNA-582 that might contribute mechanistically to the development of metabolic disorders in the older progeny.
Keywords
Article, /631/1647/767/1424, /631/45/287/1182, /38, /38/77, /82/29, /82/80, article
Sponsorship
Medical Research Council (MC_UU_12012/4)
British Heart Foundation (RG/17/12/33167)
MRC (MC_UU_00014/4)
MRC (MC_UU_00014/5)
Identifiers
s41366-021-00985-1, 985
External DOI: https://doi.org/10.1038/s41366-021-00985-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333392
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: support@repository.cam.ac.uk