• Open Access

Metabolic effects of intra-abdominal fat in GHRKO mice

Authors

  • Michal M. Masternak,

    1. College of Medicine, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32827, USA
    2. Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznań, Poland
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  • Andrzej Bartke,

    1. Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
    2. Department of Physiology, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
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  • Feiya Wang,

    1. Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
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  • Adam Spong,

    1. Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
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  • Adam Gesing,

    1. Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
    2. Department of Oncological Endocrinology, Chair of Endocrinology and Metabolic Diseases, Medical University of Lodz, Lodz, Poland
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  • Yimin Fang,

    1. Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
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  • Adam B. Salmon,

    1. Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio TX 78245, USA
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  • Larry F. Hughes,

    1. Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
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  • Teresa Liberati,

    1. Departments of Internal Medicine and Laboratory Animal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
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  • Ravneet Boparai,

    1. Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
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  • John J. Kopchick,

    1. Edison Biotechnology Institute, Department of Biomedical Sciences, Ohio University, Athens, OH 45701, USA
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  • Reyhan Westbrook

    1. Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
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Michal M. Masternak, Ph.D., University of Central Florida, Burnett School of Biomedical Sciences, College of Medicine, 6900 Lake Nona Blvd., Orlando, FL 32827, USA. Tel.: 407 266 7113; fax: 407 266 7002; e-mail: michal.masternak@ucf.edu

Summary

Mice with targeted deletion of the growth hormone receptor (GHRKO mice) are growth hormone (GH) resistant, small, obese, hypoinsulinemic, highly insulin sensitive and remarkably long-lived. To elucidate the unexpected coexistence of adiposity with improved insulin sensitivity and extended longevity, we examined effects of surgical removal of visceral (epididymal and perinephric) fat on metabolic traits related to insulin signaling and longevity. Comparison of results obtained in GHRKO mice and in normal animals from the same strain revealed disparate effects of visceral fat removal (VFR) on insulin and glucose tolerance, adiponectin levels, accumulation of ectopic fat, phosphorylation of insulin signaling intermediates, body temperature, and respiratory quotient (RQ). Overall, VFR produced the expected improvements in insulin sensitivity and reduced body temperature and RQ in normal mice and had opposite effects in GHRKO mice. Some of the examined parameters were altered by VFR in opposite directions in GHRKO and normal mice, and others were affected in only one genotype or exhibited significant genotype × treatment interactions. Functional differences between visceral fat of GHRKO and normal mice were confirmed by measurements of adipokine secretion, lipolysis, and expression of genes related to fat metabolism. We conclude that in the absence of GH signaling, the secretory activity of visceral fat is profoundly altered and unexpectedly promotes enhanced insulin sensitivity. The apparent beneficial effects of visceral fat in GHRKO mice may also explain why reducing adiposity by calorie restriction fails to improve insulin signaling or further extend longevity in these animals.

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