Metabolic effects of intra-abdominal fat in GHRKO mice - PubMed (original) (raw)

doi: 10.1111/j.1474-9726.2011.00763.x. Epub 2011 Nov 28.

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

Affiliations

Metabolic effects of intra-abdominal fat in GHRKO mice

Michal M Masternak et al. Aging Cell. 2012 Feb.

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.

© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Visceral fat content from normal and growth hormone receptor/binding protein knockout (GHRKO) male mice presented as an absolute values and percentage of body weight (n=5–6). Means ± SEM. a,b – values that do not share the same letter in the superscript are statistically significant (P<0.05).

Figure 2

Figure 2

Results of insulin tolerance test (ITT) and glucose tolerance test (GTT) in normal and growth hormone receptor/binding protein knockout (GHRKO) mice subjected to surgical visceral fat removal (VFR) or sham surgery (n=5–6).

Figure 3

Figure 3

The content of fat in (A) liver and (B) skeletal muscle from normal and growth hormone receptor/binding protein knockout (GHRKO) mice subjected to surgical visceral fat removal (VFR) or sham surgery. Results presented as a percentage of fat mass (n=8–10). Means ± SEM. a,b,c – values that do not share the same letter in the superscript are significantly different (P<0.05).

Similar articles

Cited by

References

    1. Bartke A, Wright JC, Mattison JA, Ingram DK, Miller RA, Roth GS. Extending the lifespan of long-lived mice. Nature. 2001 Nov 22;414(6862):412. - PubMed
    1. Bartke A. Insulin and aging. Cell Cycle. 2008 Nov 1;7(21):3338–3343. - PubMed
    1. Brown-Borg HM, Borg KE, Meliska CJ, Bartke A. Dwarf mice and the ageing process. Nature. 1996 Nov 7;384(6604):33. - PubMed
    1. Coschigano KT, Holland AN, Riders ME, List EO, Flyvbjerg A, Kopchick JJ. Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology. 2003 Sep;144(9):3799–3810. - PubMed
    1. Tatar M, Bartke A, Antebi A. The endocrine regulation of aging by insulin-like signals. Science. 2003 Feb 28;299(5611):1346–1351. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources