title: Altered somatotroph feedback regulation improves metabolic efficiency and limits adipose deposition in male mice.
abstract: Several transgenic mouse models with disruption in the growth hormone (GH) axis support the role of GH in augmenting metabolic homeostasis. Specifically, interest has focused on GH's lipolytic properties and ability to affect adipose deposition. Furthermore, both GH and insulin growth factor 1 (IGF-1) may also play a direct or indirect role in adipose development. The somatotroph insulin-like growth factor-1 receptor knockout (SIGFRKO) mouse with only a modest increase in serum GH and IGF-1 demonstrates less adipose tissue than controls. In order to characterize the metabolic phenotype of SIGFRKO mice, histologic analysis of fat depots confirmed a smaller average diameter of adipocytes in the SIGFRKO mice compared to controls. These changes were accompanied by an increase in lipolytic gene expression in fat depots. Indirect calorimetry performed on 6-8week old male mice and again at 25weeks of age demonstrated that SIGFRKO mice, at both ages, had a higher VO2 and increased energy expenditure when compared with controls. The calculated respiratory exchange ratio (RER) was lower in the younger SIGFRKO mice compared to controls. No differences in food consumption or in either ambulatory or total activity were seen between SIGFRKO and control mice in either age group. These studies highlight the role of GH in adipose deposition and its influence on the expression of lipolytic genes resulting in an altered metabolic state, thus providing a mechanism for the decrease in weight gain seen in the SIGFRKO mouse model.
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1616, New York, NY 10029. Electronic address: christopher.romero@mountsinai.org.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Romero
authors.affiliation: Division of Pediatric Endocrinology, Johns Hopkins University, School of Medicine, 600 North Wolfe Street, CSMC 4-106, Baltimore, MD 21287.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wolfe
authors.affiliation: Division of Pediatric Endocrinology, Johns Hopkins University, School of Medicine, 600 North Wolfe Street, CSMC 4-106, Baltimore, MD 21287.
authors.forename: Yi Ying
authors.initials: YY
authors.lastname: Law
authors.affiliation: Division of Pediatric Endocrinology, Johns Hopkins University, School of Medicine, 600 North Wolfe Street, CSMC 4-106, Baltimore, MD 21287.
authors.forename: ChenChen Z
authors.initials: CZ
authors.lastname: Costelloe
authors.affiliation: Division of Pediatric Endocrinology, University of Maryland Medical Center, 22. S. Greene St., Baltimore, MD 21201.
authors.forename: Ryan
authors.initials: R
authors.lastname: Miller
authors.affiliation: Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences, New Brunswick, NJ 08901.
authors.forename: Fredric
authors.initials: F
authors.lastname: Wondisford
authors.affiliation: Robert Wood Johnson Medical School, Rutgers Biomedical and Health Sciences, New Brunswick, NJ 08901.
authors.forename: Sally
authors.initials: S
authors.lastname: Radovick
mesh_terms: D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D002153:Calorimetry, Indirect; D025461:Feedback, Physiological / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D008066:Lipolysis / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010101:Oxygen Consumption; D052683:Somatotrophs / Q000502:physiology*
chemical_list: C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I
keywords: Adipose; Growth hormone; Indirect calorimetry