Maternal diet-induced obesity programmes cardiac dysfunction in male mice independently of post-weaning diet

Autor(es):Mostrar menos -

Loche, Elena ^{[1, 2]} ; Blackmore, Heather L. ^{[1, 2]} ; Carpenter, Asha A. ^{[1, 2]} ; Beeson, Jessica H. ^{[1, 2]} ; Pinnock, Adele ^{[1, 2]} ; Ashmore, Thomas J. ^{[1, 2]} ; Aiken, Catherine E. ^{[1, 2, 3, 4]} ; de Almeida-Faria, Juliana ^{[1, 2, 5]} ; Schoonejans, Josca M. ^{[1, 2]} ; Giussani, Dino A. ^[6] ; Fernandez-Twinn, Denise S. ^{[1, 2]} ; Ozanne, Susan E. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Cambridge, Metab Res Labs, Level 4, Box 289, Hills Rd, Cambridge CB2 OQQ - England

^[2] Addenbrookes Hosp, Addenbrookes Treatment Ctr, Wellcome Trust MRC Inst Metab Sci, MRC Metab Dis Unit, Cambridge CB2 OQQ - England

^[3] Univ Cambridge, Rosie Hosp, Dept Obstet & Gynaecol, Box 223, Cambridge CB2 0SW - England

^[4] Univ Cambridge, NIHR Cambridge Comprehens Biomed Res Ctr, Box 223, Cambridge CB2 0SW - England

^[5] Univ Estadual Campinas, Fac Med Sci, Obes & Comorbid Res Ctr, BR-13083864 Campinas, SP - Brazil

^[6] Univ Cambridge, Dept Physiol Dev & Neurosci, Downing St, Cambridge CB2 3EG - England

• Tipo de documento: Artigo Científico
• Fonte: Cardiovascular Research; v. 114, n. 10, p. 1372-1384, AUG 1 2018.
• Citações Web of Science: 17

Resumo

Aims Obesity during pregnancy increases risk of cardiovascular disease (CVD) in the offspring and individuals exposed to over-nutrition during fetal life are likely to be exposed to a calorie-rich environment postnatally. Here, we established the consequences of combined exposure to a maternal and post-weaning obesogenic diet on offspring cardiac structure and function using an established mouse model of maternal diet-induced obesity. Methods and results The impact of the maternal and postnatal environment on the offspring metabolic profile, arterial blood pressure, cardiac structure, and function was assessed in 8-week-old C57BL/6 male mice. Measurement of cardiomyocyte cell area, the transcriptional re-activation of cardiac fetal genes as well as genes involved in the regulation of contractile function and matrix remodelling in the adult heart were determined as potential mediators of effects on cardiac function. In the adult offspring: a post-weaning obesogenic diet coupled with exposure to maternal obesity increased serum insulin (P < 0.0001) and leptin levels (P < 0.0001); maternal obesity (P = 0.001) and a post-weaning obesogenic diet (P = 0.002) increased absolute heart weight; maternal obesity (P = 0.01) and offspring obesity (P = 0.01) caused cardiac dysfunction but effects were not additive; cardiac dysfunction resulting from maternal obesity was associated with re-expression of cardiac fetal genes (Myh7: Myh6 ratio; P = 0.0004), however, these genes were not affected by offspring diet; maternal obesity (P = 0.02); and offspring obesity (P = 0.05) caused hypertension and effects were additive. Conclusions Maternal diet-induced obesity and offspring obesity independently promote cardiac dysfunction and hypertension in adult male progeny. Exposure to maternal obesity alone programmed cardiac dysfunction, associated with hallmarks of pathological left ventricular hypertrophy, including increased cardiomyocyte area, upregulation of fetal genes, and remodelling of cardiac structure. These data highlight that the perinatal period is just as important as adult-onset obesity in predicting CVD risk. Therefore, early developmental periods are key intervention windows to reduce the prevalence of CVD. (AU)

• Processo FAPESP: 17/03525-8 - O papel da obesidade materna na modulação dos microRNAs hipotalâmicos da prole e consequências metabólicas associadas
• Beneficiário: Juliana de Almeida Faria
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado