Metabolic effects of intra-abdominal fat in GHRKO mice

Michal M. Masternak, Andrzej Bartke, Feiya Wang, Adam Spong, Adam Gesing, Yimin Fang, Adam B. Salmon, Larry F. Hughes, Teresa Liberati, Ravneet Boparai, John J. Kopchick, Reyhan Westbrook

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)73-81
Number of pages9
JournalAging Cell
Volume11
Issue number1
DOIs
StatePublished - Feb 1 2012

Keywords

  • Adipose tissue
  • GHRKO
  • Insulin

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Fingerprint Dive into the research topics of 'Metabolic effects of intra-abdominal fat in GHRKO mice'. Together they form a unique fingerprint.

  • Cite this

    Masternak, M. M., Bartke, A., Wang, F., Spong, A., Gesing, A., Fang, Y., Salmon, A. B., Hughes, L. F., Liberati, T., Boparai, R., Kopchick, J. J., & Westbrook, R. (2012). Metabolic effects of intra-abdominal fat in GHRKO mice. Aging Cell, 11(1), 73-81. https://doi.org/10.1111/j.1474-9726.2011.00763.x