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Animal Models

Anthropometric and glucometabolic changes in an aged mouse model of lipocalin-2 overexpression

International Journal of Obesity volume 43, pages 189–201 (2019)Cite this article

Subjects

Abstract

Background:

Lipocalin-2 (LCN2) is widely expressed in the organism with pleiotropic roles. In particular, its overexpression correlates with tissue stress conditions including inflammation, metabolic disorders, chronic diseases and cancer.

Objectives:

To assess the effects of systemic LCN2 overexpression on adipose tissue and glucose metabolism.

Subjects:

Eighteen-month-old transgenic mice with systemic LCN2 overexpression (LCN2-Tg) and age/sex-matched wild-type mice.

Methods:

Metabolic cages; histology and real-time PCR analysis; glucose and insulin tolerance tests; ELISA; flow cytometry; microPET and serum analysis.

Results:

LCN2-Tg mice were smaller compared to controls but they ate (P = 0.0156) and drank (P = 0.0057) more and displayed a higher amount of visceral adipose tissue. Furthermore, LCN2-Tg mice with body weight ≥20 g showed adipocytes with a higher cell area (P < 0.0001) and altered expression of genes involved in adipocyte differentiation and inflammation. In particular, mRNA levels of adipocyte-derived Pparg (P ≤ 0.0001), Srebf1 (P < 0.0001), Fabp4 (P = 0.056), Tnfa (P = 0.0391), Il6 (P = 0.0198), and Lep (P = 0.0003) were all increased. Furthermore, LCN2-Tg mice displayed a decreased amount of basal serum insulin (P = 0.0122) and a statistically significant impaired glucose tolerance and insulin sensitivity consistent with Slc2a2 mRNA (P ≤ 0.0001) downregulated expression. On the other hand, Insr mRNA (P ≤ 0.0001) was upregulated and correlated with microPET analysis that demonstrated a trend in reduced whole-body glucose consumption and MRGlu in the muscles and a significantly reduced MRGlu in brown adipose tissue (P = 0.0247). Nevertheless, an almost nine-fold acceleration of hexokinase activity was observed in the LCN2-Tg mice liver compared to controls (P = 0.0027). Moreover, AST and ALT were increased (P = 0.0421 and P = 0.0403, respectively), which indicated liver involvement also demonstrated by histological staining.

Conclusions:

We show that LCN2 profoundly impacts adipose tissue size and function and glucose metabolism, suggesting that LCN2 should be considered as a risk factor in ageing for metabolic disorders leading to obesity.

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Acknowledgements

We wish to thank Katia Cortese (University of Genoa, Italy) for the lipid droplets analysis. This work was partially supported by funds from Italian Space Agency.

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Authors and Affiliations

  1. Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy

    Elisa Principi, Andrea Papait, Roberta Pece, Irena Maric & Sara Tavella

  2. IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Elisa Principi, Ambra Buschiazzo, Andrea Papait, Patrizio Castagnola, Delfina Costa, Roberta Pece, Gianmario Sambuceti & Sara Tavella

  3. Dipartimento di Scienze della Salute, Università degli Studi di Genova, Genova, Italy

    Ambra Buschiazzo & Gianmario Sambuceti

  4. Dipartimento di Matematica, Università degli Studi di Genova, Genova, Italy

    Mara Scussolini

  5. CNR Istituto di Bioimmagini e Fisiologia Molecolare, Milano, Italy

    Cecilia Marini

  6. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy

    Felice Strollo

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Correspondence to Sara Tavella.

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Principi, E., Buschiazzo, A., Papait, A. et al. Anthropometric and glucometabolic changes in an aged mouse model of lipocalin-2 overexpression. Int J Obes 43, 189–201 (2019). https://doi.org/10.1038/s41366-018-0171-5

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