ffects of maternal diet-induced obesity on metabolic disorders and age-associated miRNA expression in the liver of male mouse offsprin

Autor(es):Mostrar menos -

Mennitti, Lais Vales ^{[1, 2, 3]} ; Carpenter, Asha A. M. ^{[2, 3]} ; Loche, Elena ^{[2, 3]} ; Pantaleao, Lucas C. ^{[2, 3]} ; Fernandez-Twinn, Denise S. ^{[2, 3]} ; Schoonejans, Josca M. ^{[2, 3]} ; Blackmore, Heather L. ^{[2, 3]} ; Ashmore, Thomas J. ^{[2, 3]} ; Pisani, Luciana Pellegrini ^{[1, 2, 3]} ; Tadross, John A. ^{[4, 2, 3]} ; Hargreaves, Iain ^[5] ; Ozanne, Susan E. ^{[2, 3]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Biosci, Lab Nutr & Endocrine Physiol, BR-11015020 Santos, SP - Brazil

^[2] Univ Cambridge, Metab Res Labs, Cambridge CB2 OQQ - England

^[3] Univ Cambridge, MRC Metab Dis Unit, Cambridge CB2 OQQ - England

^[4] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP - England

^[5] Liverpool John Moores Univ, Dept Pharm & Biomol Sci, Byrom St, Liverpool L3 5UA, Merseyside - England

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Obesity; v. 46, n. 2 OCT 2021.
• Citações Web of Science: 0

Resumo

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, Tgf beta 1, Map3k14, and Col1a1 in the liver. Decreased levels of Bcl-2, p-AMPK alpha, total AMPK alpha 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. (AU)

• Processo FAPESP: 19/22635-4 - O efeito da obesidade materna sob a saúde da prole com foco no papel do microRNA do tecido adiposo
• Beneficiário: Luciana Pellegrini Pisani
• Modalidade de apoio: Bolsas no Exterior - Pesquisa
• Processo FAPESP: 14/10683-0 - Efeito da ingestão materna de diferentes ácidos graxos durante a gestação e lactação nas modificações epigenéticas e estado pró-inflamatório do feto e prole com 21 dias de vida
• Beneficiário: Laís Vales Mennitti
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/16637-9 - O papel dos miRNAs na programação do acúmulo de lipídeos no fígado dos descendentes induzidos a obesidade pela dieta materna
• Beneficiário: Laís Vales Mennitti
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado