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Research article

Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes

Connie Hung, Casey Bronec, Eleonora Napoli, James Graham, Kimber L. Stanhope, Ilaria Marsilio, Maria Cecilia Giron, Peter J. Havel, Cecilia Giulivi
Biochemical Journal Feb 14, 2018, 475 (3) 649-662; DOI: 10.1042/BCJ20170899
Connie Hung
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.
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Casey Bronec
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.
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Eleonora Napoli
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.
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James Graham
Department of Nutrition, University of California, Davis, CA 95616, U.S.A.
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Kimber L. Stanhope
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.Department of Nutrition, University of California, Davis, CA 95616, U.S.A.
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Ilaria Marsilio
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.Department of Pharmaceutical and Pharmacological Sciences, Pharmacology Building, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy
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Maria Cecilia Giron
Department of Pharmaceutical and Pharmacological Sciences, Pharmacology Building, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy
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Peter J. Havel
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.Department of Nutrition, University of California, Davis, CA 95616, U.S.A.
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Cecilia Giulivi
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, U.S.A.Medical Investigations of Neurodevelopmental Disorders (M. I. N. D.) Institute, University of California, Davis, CA 95817, U.S.A.
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  • For correspondence: cgiulivi@ucdavis.edu
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Abstract

Ileal interposition (IT) surgery delays the onset of diabetes in a rat model of type-2 diabetes (UCD-T2DM). Here, to gain a deeper understanding of the molecular events underlying the effects of IT surgery, we examined the changes in the proteome of four white adipose depots (retroperitoneal, mesenteric, inguinal, and epididymal) and plasma-free fatty acid profile in pre-diabetic rats 1.5 months following IT or sham surgery. The IT-mediated changes were exerted mainly in mesenteric fat and spanned from delayed adipocyte maturation to a neuroendocrine remodeling. Conversely, inguinal, retroperitoneal, and epididymal depots showed opposite trends consistent with increased adipocyte maturation and adipogenesis development prior to overt signs of diabetes, probably orchestrated by peroxisome proliferator-activated receptor gamma signaling and higher plasma n-6/n-3 free fatty acid ratios. The resulting scenario suggests a targeted use of surgical strategies that seek to delay or improve diabetes in order to manipulate adipose depot-specific responses to maximize the duration and beneficial effects of the surgery.

  • lipidomics
  • obesity
  • proteomics
  • rat models
  • type 2 diabetes
  • white adipose tissue
  • Abbreviations

    ACL,
    average chain length;
    D5D,
    delta-5 desaturase;
    D6D,
    delta-6 desaturase;
    DBI,
    double bond index;
    ER,
    endoplasmic reticulum;
    FFA,
    free fatty acids;
    GLP-1,
    glucagon-like peptide-1;
    Hb,
    hemoglobin;
    Insm2,
    insulinoma-associated protein 2;
    IT,
    ileal interposition;
    LD,
    lipid droplets;
    MS,
    mass spectrometry;
    PI,
    peroxidizability index;
    PPARγ,
    peroxisome proliferator-activated receptor gamma;
    PUFA,
    polyunsaturated fats;
    T2D,
    type 2 diabetes;
    T2DM,
    type 2 diabetes mellitus;
    TCA,
    tricarboxylic acid;
    TG,
    triglycerides;
    WAT,
    white adipose tissue
    • © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
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    February 2018

    Volume: 475 Issue: 3

    Biochemical Journal: 475 (3)
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    Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes
    Connie Hung, Casey Bronec, Eleonora Napoli, James Graham, Kimber L. Stanhope, Ilaria Marsilio, Maria Cecilia Giron, Peter J. Havel, Cecilia Giulivi
    Biochemical Journal Feb 2018, 475 (3) 649-662; DOI: 10.1042/BCJ20170899
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    Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes
    Connie Hung, Casey Bronec, Eleonora Napoli, James Graham, Kimber L. Stanhope, Ilaria Marsilio, Maria Cecilia Giron, Peter J. Havel, Cecilia Giulivi
    Biochemical Journal Feb 2018, 475 (3) 649-662; DOI: 10.1042/BCJ20170899

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    Keywords

    lipidomics
    obesity
    proteomics
    rat models
    type 2 diabetes
    white adipose tissue

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