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Gender-specific effects on food intake but no inhibition of age-related fat accretion in transgenic mice overexpressing human IGFBP-2 lacking the Cardin-Weintraub sequence motif

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Journal of Cell Communication and Signaling Aims and scope

Abstract

IGFBP-2 affects growth and metabolism and is thought to impact on energy homeostasis and the accretion of body fat via its heparin binding domains (HBD). In order to assess the function of the HBD present in the linker domain (HBD1) we have generated transgenic mice overexpressing mutant human IGFBP-2 lacking the PKKLRP sequence and carrying a PNNLAP sequence instead. Transgenic mice expressed high amounts of human IGFBP-2, while endogenous IGFBP-2 or IGF-I serum concentrations were not affected. In both genders we performed a longitudinal analysis of growth and metabolism including at least 4 separate time points between the age of 10 and 52 weeks. Body composition was assessed by nuclear magnetic resonance (NMR) analysis. Food intake was recorded by an automated online-monitoring. We describe negative effects of mutant human IGFBP-2 on body weight, longitudinal growth and lean body mass (p < 0.05). Very clearly, negative effects of mutant IGFBP-2 were not observed for fat mass accretion throughout life. Instead, relative fat mass was increased in transgenic mice of both genders (p < 0.05). In male mice transgene expression significantly increased absolute mass of total body fat over all age groups (p < 0.05). Food intake was increased in female but decreased in male transgenic mice at an age of 11 weeks. Thus our study clearly provides gender- and time-specific effects of HBD1-deficient hIGFBP-2 (H1d-BP-2) on fat mass accretion and food intake. While our data are in principal agreement with current knowledge on the role of HB-domains for fat accretion we now may also speculate on a role of HBD1 for the control of eating behavior.

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Acknowledgments

We are grateful to Tamara Holy and Eckhard Wolf (Gene Center, Munich, Germany) for microinjection of the transgenic expression vector and development of the H1d-BP2 mouse model. VCR was supported by the NHMRC of Australia (Project Grant, # 1008062). AH was supported by the Deutsche Forschungsgemeinschaft (DFG HO2003/1-6).

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Authors and Affiliations

  1. Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, A.-Scheunert-Allee 114-116, D14558, Nuthetal, Germany

    Petra Wiedmer, Franziska Schwarz & Birgit Große

  2. Institute for Genome Biology, Leibniz-Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany

    Nancy Schindler & Andreas Hoeflich

  3. Institute for Genetics and Biometry, Leibniz-Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany

    Armin Tuchscherer

  4. Hormone Research, Murdoch Childrens Research Institute, Department of Paediatrics University of Melbourne, Royal Children’s Hospital, Parkville, VIC, Australia

    Vincenzo C. Russo

  5. Metabolic Disease Institute, Division of Endocrinology, Department of Medicine, University of Cincinnati, Cincinnati, OH, 45226, USA

    Matthias H. Tschöp

Authors
  1. Petra Wiedmer
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  2. Franziska Schwarz
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  3. Birgit Große
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  4. Nancy Schindler
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  6. Vincenzo C. Russo
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  7. Matthias H. Tschöp
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  8. Andreas Hoeflich
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Correspondence to Andreas Hoeflich.

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Wiedmer, P., Schwarz, F., Große, B. et al. Gender-specific effects on food intake but no inhibition of age-related fat accretion in transgenic mice overexpressing human IGFBP-2 lacking the Cardin-Weintraub sequence motif. J. Cell Commun. Signal. 9, 143–150 (2015). https://doi.org/10.1007/s12079-015-0264-z

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  • DOI: https://doi.org/10.1007/s12079-015-0264-z

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