ESPE Abstracts (2018) 89 FC4.3

The Reduction in Longitudinal Growth Induced By PAPP-A2 Deficiency is Associated with Reduced Body Weight, Increased Energy Expenditure and Behavior Modification

Juan Suáreza,b,c, Patricia Riverad, Antonio Vargasa,b,c, Leticia Rubioe, Fernando Rodríguez de Fonsecaa,b,c, Julie Chowend,f,g,h & Jesús Argented,i,j,g,k


aInstituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain; bUGC Salud Mental, Universidad de Málaga, Málaga, Spain; cHospital Universitario Regional de Málaga, Málaga, Spain; dDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain; eDepartment of Anatomy, and Forensic and Legal Medicine, Universidad de Málaga, Málaga, Spain; fLa ÑPrincesa Institute of Research, Madrid, Spain; gCentro de Investigación Biomédica en Red de Fisiopatologia de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; hIMDEA Food Institute, Madrid, Spain; iLa Princesa Reasearch Institute, Madrid, Spain; jDepartment of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain; kIMDEA Institute of Research, Madrid, Spain


Background: Pregnancy associated plasma protein (PAPP)-A2 is an insulin-like growth factor (IGF) binding protein (BP) protease that regulates IGF-1 availability, affecting postnatal growth. We have recently reported the first mutations in human PAPP-A2 causing short stature and changes in bone size and mineral density. However, the IGF system is involved in diverse physiological functions and to date it is unknown how mutations in PAPP-A2, which significantly reduce free IGF levels, might affect these functions.

Objective: The present study aimed to characterize the effects of constitutive papp-a2 gene deletion on energy metabolism in adult male and female mice.

Results: Mice homozygous for a papp-a2 gene deletion had reduced body length (5–7% reduction) and low body weight (12–16% reduction) from postnatal day (PND) 24 to PND 85 compared to wild-type mice. At 6 months of age, in addition to reduced body length and weight, these papp-a2 gene knock-out (KO) mice also had a reduction in bone (femur and tibia) weight and length. Analysis in metabolic cages indicated that PAPP-A2 deficiency increased energy expenditure (kcal/day per kg body weight) and altered [VO2] consumption and [VCO2] production (mL/min per kg body weight), resulting in an increase in respiratory quotient [VCO2/VO2]. Additionally, adult papp-a2 KO mice had a reduction in calorie intake (kcal/g body weight) and locomotor activity, with this reaching significance in males, and an increase in rearing (vertical activity) in females, suggesting that behavior may be affected.

Conclusion: These results further support a role of PAPP-A2 activity in the regulation of postnatal growth and body weight gain and suggest that this protease may be involved in the mediation of IGF-1’s effects on energy expenditure and possibly behavior.

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