Title

Key Regulators Of Mitochondrial Biogenesis Are Increased In Kidneys Of Growth Hormone Receptor Knockout (Ghrko) Mice

Keywords

Calorie restriction; Growth hormone receptor knockout (GHRKO) mice; Kidneys; Mitochondrial biogenesis; Proteins; Skeletal muscles; Visceral fat

Abstract

The growth hormone receptor knockout (GHRKO) mice are remarkably long-lived and highly insulin sensitive. Alterations in mitochondrial biogenesis are associated with aging and various metabolic derangements. We have previously demonstrated increased gene expression of key regulators of mitochondriogenesis in kidneys, hearts and skeletal muscles of GHRKO mice. The aim of the present study was to quantify the protein levels of the following regulators of mitochondriogenesis: peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), AMP-activated protein kinase α (AMPKα), phospho-AMPKα (p-AMPKα), sirtuin-3 (SIRT-3), endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), nuclear respiratory factor-1 (NRF-1) and mitofusin-2 (MFN-2) in skeletal muscles and kidneys of GHRKOs in comparison to normal mice. We also were interested in the effects of calorie restriction (CR) and visceral fat removal (VFR) on these parameters. Both CR and VFR improve insulin sensitivity and can extend life span. Results: The renal levels of PGC-1α, AMPKα, p-AMPKα, SIRT-3, eNOS, p-eNOS and MFN-2 were increased in GHRKOs. In the GHRKO skeletal muscles, only MFN-2 was increased. Levels of the examined proteins were not affected by CR (except for PGC-1α and p-eNOS in skeletal muscles) or VFR. Conclusion: GHRKO mice have increased renal protein levels of key regulators of mitochondriogenesis, and this may contribute to increased longevity of these knockouts. © 2011 John Wiley & Sons, Ltd.

Publication Date

8-1-2011

Publication Title

Cell Biochemistry and Function

Volume

29

Issue

6

Number of Pages

459-467

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1002/cbf.1773

Socpus ID

80051672158 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/80051672158

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