The role of transplanted visceral fat from the long-lived growth hormone receptor knockout mice on insulin signaling

Geroscience. 2017 Feb;39(1):51-59. doi: 10.1007/s11357-017-9957-y. Epub 2017 Jan 18.

Abstract

Growth hormone receptor knockout mice (GHRKO) are characterized by high insulin sensitivity and extended lifespan. Interestingly, the secretory activity of visceral fat in GHRKO mice is altered, stimulating whole body insulin sensitivity. In this study, we transplanted normal (N) mice with visceral fat pads from GHRKO or N mice to determine the role of visceral fat on the insulin signaling. We found that the transplant of visceral fat from GHRKO mice to N mice (N-GHRKO) improved whole body insulin sensitivity when comparing with sham-operated mice (N-S) and with mice that received visceral fat from N mice (N-N). This was associated with increased hepatic insulin sensitivity as observed by the increased phosphorylated insulin receptor and increased hepatic expression of Pparα and Pparγ. In conclusion, we demonstrated that visceral fat transplant from GHRKO mice into normal mice enhanced insulin sensitivity and glucose tolerance. These results further confirm the differential physiological role played by visceral adipose tissue from GH receptor deficient mice, indicating that the increase of this fat depot can be associated with beneficial effects on insulin signaling and longevity.

Keywords: GHR; GHRKO; Insulin resistance; Longevity; Type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gene Expression Regulation
  • Glucose Tolerance Test
  • Growth Hormone / metabolism
  • Insulin / metabolism*
  • Insulin Resistance / genetics*
  • Intra-Abdominal Fat / transplantation*
  • Longevity
  • Male
  • Mice
  • Mice, Knockout
  • Phosphorylation
  • RNA / genetics*
  • Random Allocation
  • Receptors, Somatotropin / metabolism*
  • Signal Transduction

Substances

  • Insulin
  • Receptors, Somatotropin
  • RNA
  • Growth Hormone