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Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs

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Abstract

The aim of this study was to elucidate the relative impact of three phenotypes often used to characterize obesity on perturbation of molecular pathways involved in obesity. The three obesity-related phenotypes are (1) body mass index (BMI), (2) amount of subcutaneous adipose tissue (SATa), and (3) amount of retroperitoneal adipose tissue (RPATa). Although it is generally accepted that increasing amount of RPATa is ‘unhealthy’, a direct comparison of the relative impact of the three obesity-related phenotypes on gene expression has, to our knowledge, not been performed previously. We have used multiple linear models to analyze altered gene expression of selected obesity-related genes in tissues collected from 19 female pigs phenotypically characterized with respect to the obesity-related phenotypes. Gene expression was assessed by high-throughput qPCR in RNA from liver, skeletal muscle and abdominal adipose tissue. The stringent statistical approach used in the study has increased the power of the analysis compared to the classical approach of analysis in divergent groups of individuals. Our approach led to the identification of key components of cellular pathways that are modulated in the three tissues in association with changes in the three obesity-relevant phenotypes (BMI, SATa and RPATa). The deregulated pathways are involved in biosynthesis and transcript regulation in adipocytes, in lipid transport, lipolysis and metabolism, and in inflammatory responses. Deregulation seemed more comprehensive in liver (23 genes) compared to abdominal adipose tissue (10 genes) and muscle (3 genes). Notably, the study supports the notion that excess amount of intra-abdominal adipose tissue is associated with a greater metabolic disease risk. Our results provide molecular support for this notion by demonstrating that increasing amount of RPATa has a higher impact on perturbation of cellular pathways influencing obesity and obesity-related metabolic traits compared to increase in BMI and amount of SATa.

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Author notes

  1. Susanna Cirera and Merete Fredholm have contributed equally.

Authors and Affiliations

  1. Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 3, 1870, Frederiksberg C, Denmark

    Caroline M. Junker Mentzel, Tainã Figueiredo Cardoso, Mette Juul Jacobsen, Claus Bøttcher Jørgensen, Susanna Cirera & Merete Fredholm

  2. Department of Animal Genetics, Center for Research in Agricultural Genomics (CSIC-IRTA-UAB-UB), Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Tainã Figueiredo Cardoso

  3. Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, 1014, Copenhagen K, Denmark

    Christian Bressen Pipper

Authors
  1. Caroline M. Junker Mentzel
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  2. Tainã Figueiredo Cardoso
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  3. Christian Bressen Pipper
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  4. Mette Juul Jacobsen
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  5. Claus Bøttcher Jørgensen
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  6. Susanna Cirera
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  7. Merete Fredholm
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Corresponding author

Correspondence to Merete Fredholm.

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Funding

This study was supported by the Danish Independent Research Council Grant number DFF 1335-00127. Tainã Figueiredo Cardoso was supported by an Erasmus+ Grant for superior education 2015 from the European Commission.

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The Danish Animal Experiments Inspectorate approved all experimental procedures and animal care and maintenance have been conducted according to the Danish “Animal Maintenance Act” (Act 432 dated 09/06/2004).

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Communicated by S. Hohmann.

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Mentzel, C.M.J., Cardoso, T.F., Pipper, C.B. et al. Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs. Mol Genet Genomics 293, 129–136 (2018). https://doi.org/10.1007/s00438-017-1369-2

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  • DOI: https://doi.org/10.1007/s00438-017-1369-2

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