Maternal obesity programs reduced leptin signaling in the pituitary and altered GH/IGF1 axis function leading to increased adiposity in adult sheep offspring

• Published in: PloS one Vol. 12; no. 8; p. e0181795
• Main Authors: Tuersunjiang, Nuermaimaiti, Odhiambo, John F, Shasa, Desiree R, Smith, Ashley M, Nathanielsz, Peter W, Ford, Stephen P
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03-08-2017; Public Library of Science (PLoS)
• Subjects: 11β-Hydroxysteroid dehydrogenase; Adipose tissue; Adiposity; Adrenocorticotropic Hormone - metabolism; Animals; Arcuate nucleus; Biology and Life Sciences; Body composition; Body composition (biology); Cortisol; Cortisone; Dehydrogenase; Down-Regulation; Feeding; Female; Gene expression; Glucose; Growth hormone; Growth Hormone - blood; Growth hormones; Hexose; Hydrocortisone - metabolism; Hyperphagia; Hypothalamus; Insulin; Insulin resistance; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Leptin; Leptin - metabolism; Liver; Liver - metabolism; Male; Medicine and Health Sciences; Mothers; Nuclei; Obesity; Offspring; Phosphate; Phosphates; Physiological aspects; Pituitary; Pituitary Gland - cytology; Pituitary Gland - metabolism; Pituitary hormones; Pregnancy; Research and Analysis Methods; Rodents; Secretion; Sheep; Signal Transduction; Stimulation; United States > US; Wyoming
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0181795

Studies in rodents highlight a role for leptin in stimulation of pituitary growth hormone (GH) secretion, with an impact on body composition regulation. We have reported that maternal obesity (MO) during ovine pregnancy results in hyperphagia, glucose-insulin dysregulation, increased adiposity, hypercortisolemia and hyperleptinemia in mature offspring subjected to a bout of ad libitum feeding. We hypothesized that MO reduces leptin signaling in the pituitary and down regulates the GH/IGF1 axis and increases circulating cortisol leading to increased adiposity in their adult offspring. Male lambs born to MO (n = 6) or control (CON, n = 6) ewes were fed only to requirements until placed on a 12 week ad libitum feeding trial at maturity. The pituitary, hypothalamic arcuate nucleus, and liver were collected at necropsy and mRNA and protein expression determined. Plasma cortisol concentrations were increased (P<0.05) in MO vs. CON offspring at the end of the feeding trial. Further, serum concentrations of IGF1 decreased (P<0.01) and GH tended to decrease (P<0.08) in MO vs. CON offspring. Pituitary mRNA and leptin receptor protein expression were decreased in MO vs. CON offspring in association with decreased GH mRNA expression, and decreased IGF1 mRNA and protein expression in liver. Liver 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) expression was increased (P<0.01) and its cofactor hexose-6-phosphate dehydrogenase tended to increase (P<0.06) in MO vs. CON offspring. 11βHSD2 expression remained unchanged. These data indicate that MO induced an increase in liver conversion of cortisone to cortisol in adult offspring and support a role for leptin signaling in the pituitary in mediating offspring adiposity.