title: Metabolic impact of adult-onset, isolated, growth hormone deficiency (AOiGHD) due to destruction of pituitary somatotropes.
abstract: Growth hormone (GH) inhibits fat accumulation and promotes protein accretion, therefore the fall in GH observed with weight gain and normal aging may contribute to metabolic dysfunction. To directly test this hypothesis a novel mouse model of adult onset-isolated GH deficiency (AOiGHD) was generated by cross breeding rat GH promoter-driven Cre recombinase mice (Cre) with inducible diphtheria toxin receptor mice (iDTR) and treating adult Cre(+/-),iDTR(+/-) offspring with DT to selectively destroy the somatotrope population of the anterior pituitary gland, leading to a reduction in circulating GH and IGF-I levels. DT-treated Cre(-/-),iDTR(+/-) mice were used as GH-intact controls. AOiGHD improved whole body insulin sensitivity in both low-fat and high-fat fed mice. Consistent with improved insulin sensitivity, indirect calorimetry revealed AOiGHD mice preferentially utilized carbohydrates for energy metabolism, as compared to GH-intact controls. In high-fat, but not low-fat fed AOiGHD mice, fat mass increased, hepatic lipids decreased and glucose clearance and insulin output were impaired. These results suggest the age-related decline in GH helps to preserve systemic insulin sensitivity, and in the context of moderate caloric intake, prevents the deterioration in metabolic function. However, in the context of excess caloric intake, low GH leads to impaired insulin output, and thereby could contribute to the development of diabetes.
authors.affiliation: Research and Development Division, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois, United States of America.
authors.forename: Raul M
authors.initials: RM
authors.lastname: Luque
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: José
authors.initials: J
authors.lastname: Córdoba-Chacón
authors.forename: Papasani V
authors.initials: PV
authors.lastname: Subbaiah
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buch
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Hugo
authors.initials: H
authors.lastname: Vankelecom
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Kineman
mesh_terms: D017668:Age of Onset; D000818:Animals; D050260:Carbohydrate Metabolism; D004032:Diet; D004195:Disease Models, Animal; D002149:Energy Intake; D004734:Energy Metabolism; D013006:Growth Hormone / Q000172:deficiency*; D066257:Heparin-binding EGF-like Growth Factor; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000172:deficiency; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D010903:Pituitary Gland, Anterior; D051381:Rats; D052683:Somatotrophs / Q000378:metabolism*
chemical_list: C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone