Depot- and sex-specific effects of maternal obesity in offspring's adipose tissue.
According to the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term programming of individual body weight (BW) setpoint. In particular, maternal obesity, excessive nutrition, and accelerated growth in neonates have been shown to sensitize offspring to obesity. The white adipose tissue may represent a prime target of metabolic programming induced by maternal obesity. In order to unravel the underlying mechanisms, we have developed a rat model of maternal obesity using a high-fat (HF) diet (containing 60% lipids) before and during gestation and lactation. At birth, newborns from obese dams (called HF) were normotrophs. However, HF neonates exhibited a rapid weight gain during lactation, a key period of adipose tissue development in rodents. In males, increased BW at weaning (+30%) persists until 3months of age. Nine-month-old HF male offspring was normoglycemic but showed mild glucose intolerance, hyperinsulinemia, and hypercorticosteronemia. Despite no difference in BW and energy intake, HF adult male offspring was predisposed to fat accumulation showing increased visceral (gonadal and perirenal) depots weights and hyperleptinemia. However, only perirenal adipose tissue depot exhibited marked adipocyte hypertrophy and hyperplasia with elevated lipogenic (i.e. sterol-regulated element binding protein 1 (Srebp1), fatty acid synthase (Fas), and leptin) and diminished adipogenic (i.e. peroxisome proliferator-activated receptor gamma (Pparγ), 11β-hydroxysteroid dehydrogenase type 1 (11β-Hds1)) mRNA levels. By contrast, very few metabolic variations were observed in HF female offspring. Thus, maternal obesity and accelerated growth during lactation program offspring for higher adiposity via transcriptional alterations of visceral adipose tissue in a depot- and sex-specific manner.
Univ. LilleEA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France.
Simon
S
Lecoutre
Univ. LilleEA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France.
Barbara
B
Deracinois
Univ. LilleEA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France.
Christine
C
Laborie
Univ. LilleEA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France.
Delphine
D
Eberlé
Univ. LilleEA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France.
Céline
C
Guinez
INRAUMR1198 Biologie du Développement et Reproduction, F-78350 Jouy-en-Josas, France.
Polina E
PE
Panchenko
Univ. LilleEA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France.
Jean
J
Lesage
Univ. LilleEA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France.
Didier
D
Vieau
INRAUMR1198 Biologie du Développement et Reproduction, F-78350 Jouy-en-Josas, France UVSQUniversité Versailles-Saint-Quentin-en-Yvelines, Versailles, France.
Claudine
C
Junien
INRAUMR1198 Biologie du Développement et Reproduction, F-78350 Jouy-en-Josas, France.
Anne
A
Gabory
Univ. LilleEA4489, Équipe Malnutrition Maternelle et Programmation des Maladies Métaboliques, F59000 Lille, France christophe.breton@univ-lille1.fr.
Christophe
C
Breton
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D003345:Corticosterone / Q000097:blood; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism; D007774:Lactation / Q000378:metabolism*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D009765:Obesity / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D012737:Sex Factors; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain / Q000502:physiology*
D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; D003345:Corticosterone
adipocyte size; developmental origin of health and disease; dimorphism; gene expression; high-fat diet; visceral adiposity