Ouma Cissé1,2, Isabelle Fajardy1,3, Fabien Delahaye1,4, Anne Dickes1, Valérie Montel1, Emmanuelle Moitrot1,3, Christophe Breton1, Didier Vieau1,5, Christine Laborie6. 1. Division of Maternal Malnutrition, Department of Perinatal Environment and Health, Lille University, Lille, France. 2. Center for Cell Biology and Cutaneous Research, Queen Mary University of London, 4 Newark Street, London, E1 2AT, UK. 3. Division Biochemistry and Molecular Biology, Biology and Pathology Center, Lille, France. 4. Departments of Genetics and Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA. 5. INSERM UMR-S1172, Alzheimer and Tauopathies, Labex DISTALZ, Lille University, Lille, France. 6. Division of Maternal Malnutrition, Department of Perinatal Environment and Health, Lille University, Lille, France. christine.laborie@univ-lille1.fr.
Abstract
PURPOSE: Poor maternal nutrition sensitises to the development of metabolic diseases and obesity in adulthood over several generations. The prevalence increases when offspring is fed with a high-fat (HF) diet after weaning. This study aims to determine whether such metabolic profiles can be transmitted to the second generation and even aggravated when the mothers were exposed to overnutrition, with attention to potential sex differences. METHODS: Pregnant Wistar rats were subjected to ad libitum (control) or 70% food-restricted diet (FR) during gestation (F0). At weaning, F1 females were allocated to three food protocols: (1) standard diet prior to and throughout gestation and lactation, (2) HF diet prior to and standard diet throughout gestation and lactation, and (3) HF diet prior to and throughout gestation and lactation. F2 offspring was studied between 16 and 32 weeks of age. RESULTS: FR-F2 offspring on standard diet showed normal adiposity and had no significant metabolic alterations in adulthood. Maternal HF diet resulted in sex-specific effects with metabolic disturbances more apparent in control offspring exposed to HF diet during gestation and lactation. Control offspring displayed glucose intolerance associated with insulin resistance in females. Female livers overexpressed lipogenesis genes and those of males the genes involved in lipid oxidation. Gene expression was significantly attenuated in the FR livers. Increased physical activity associated with elevated corticosterone levels was observed in FR females on standard diet and in all females from overnourished mothers. CONCLUSIONS: Maternal undernutrition during gestation (F0) improves the metabolic health of second-generation offspring with more beneficial effects in females.
PURPOSE: Poor maternal nutrition sensitises to the development of metabolic diseases and obesity in adulthood over several generations. The prevalence increases when offspring is fed with a high-fat (HF) diet after weaning. This study aims to determine whether such metabolic profiles can be transmitted to the second generation and even aggravated when the mothers were exposed to overnutrition, with attention to potential sex differences. METHODS: Pregnant Wistar rats were subjected to ad libitum (control) or 70% food-restricted diet (FR) during gestation (F0). At weaning, F1 females were allocated to three food protocols: (1) standard diet prior to and throughout gestation and lactation, (2) HF diet prior to and standard diet throughout gestation and lactation, and (3) HF diet prior to and throughout gestation and lactation. F2 offspring was studied between 16 and 32 weeks of age. RESULTS: FR-F2 offspring on standard diet showed normal adiposity and had no significant metabolic alterations in adulthood. Maternal HF diet resulted in sex-specific effects with metabolic disturbances more apparent in control offspring exposed to HF diet during gestation and lactation. Control offspring displayed glucose intolerance associated with insulin resistance in females. Female livers overexpressed lipogenesis genes and those of males the genes involved in lipid oxidation. Gene expression was significantly attenuated in the FR livers. Increased physical activity associated with elevated corticosterone levels was observed in FR females on standard diet and in all females from overnourished mothers. CONCLUSIONS: Maternal undernutrition during gestation (F0) improves the metabolic health of second-generation offspring with more beneficial effects in females.
Entities:
Keywords:
Growth; Metabolism; Multigenerational programming; Sex dimorphism