Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Nutrition and Dietetics,Endocrinology, Diabetes and Metabolism,Medicine (miscellaneous)
Reference70 articles.
1. Apovian CM. Obesity: definition, comorbidities, causes, and burden. Am J Manag Care. 2016;22:s176–s185.
2. NHS Digital. Statistics on Obesity, Physical Activity and Diet, England, 2019. Part 3: Adult overweight and obesity. https://digital.nhs.uk/data-and-information/publications/statistical/statistics-on-obesity-physical-activity-and-diet/statistics-on-obesity-physical-activity-and-diet-england-2019/part-3-adult-obesity (2019). Accessed 27 Apr 2020.
3. NMPA Project Team. National Maternity and Perinatal Audit: Clinical Report 2019. Based on births in NHS maternity services between 1 April 2016 and 31 March 2017. London: RCOG; 2019.
4. Nicholas LM, Morrison JL, Rattanatray L, Zhang S, Ozanne SE, McMillen IC. The early origins of obesity and insulin resistance: timing, programming and mechanisms. Int J Obes. 2016;40:229–38.
5. Elshenawy S, Simmons R. Maternal obesity and prenatal programming. Mol Cell Endocrinol. 2016;435:2–6.
Cited by
12 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献