title: Somatostatin Agonist Pasireotide Promotes a Physiological State Resembling Short-Day Acclimation in the Photoperiodic Male Siberian Hamster (Phodopus sungorus).
abstract: The timing of growth in seasonal mammals is inextricably linked to food availability. This is exemplified in the Siberian hamster (Phodopus sungorus), which uses the annual cycle of photoperiod to optimally programme energy expenditure in anticipation of seasonal fluctuations in food resources. During the autumn, energy expenditure is progressively minimised by physiological adaptations, including a 30% reduction in body mass, comprising a reduction in both fat and lean tissues. However, the mechanistic basis of this adaptation is still unexplained. We hypothesised that growth hormone (GH) was a likely candidate to underpin these reversible changes in body mass. Administration of pasireotide, a long-acting somatostatin receptor agonist developed for the treatment of acromegaly, to male hamsters under a long-day (LD) photoperiod produced a body weight loss. This comprised a reduction in lean and fat mass, including kidneys, testes and brown adipose tissue, typically found in short-day (SD) housed hamsters. Furthermore, when administered to hamsters switched from SD to LD, pasireotide retarded the body weight increase compared to vehicle-treated hamsters. Pasireotide did not alter photoperiod-mediated changes in hypothalamic energy balance gene expression but altered the expression of Srif mRNA expression in the periventricular nucleus and Ghrh mRNA expression in the arcuate nucleus consistent with a reduction in GH feedback and concurrent with reduced serum insulin-like growth factor-1. Conversely, GH treatment of SD hamsters increased body mass, which included increased mass of liver and kidneys. Together, these data indicate a role for the GH axis in the determination of seasonal body mass of the Siberian hamster.
authors.affiliation: Rowett Institute for Nutrition and Health, University of Aberdeen, Aberdeen, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Dumbell
authors.affiliation: University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Scherbarth
authors.affiliation: University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Diedrich
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: H A
authors.initials: HA
authors.lastname: Schmid
authors.affiliation: University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Steinlechner
authors.affiliation: Rowett Institute for Nutrition and Health, University of Aberdeen, Aberdeen, UK.
authors.forename: P
authors.initials: P
authors.lastname: Barrett
mesh_terms: D000064:Acclimatization / Q000187:drug effects / Q000502:physiology; D002001:Adipose Tissue, Brown; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D006224:Cricetinae; D013006:Growth Hormone / Q000502:physiology*; D008297:Male; D020644:Midline Thalamic Nuclei / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects / Q000502:physiology*; D017111:Phodopus / Q000502:physiology*; D017440:Photoperiod; D017481:Receptors, Somatostatin / Q000819:agonists*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology*
chemical_list: D017481:Receptors, Somatostatin; D013004:Somatostatin; D013006:Growth Hormone; C517782:pasireotide
keywords: body weight; brown adipose tissue; circadian; growth hormone; neuroendocrine; pituitary; seasonality