Research Paper Volume 12, Issue 4 pp 3473—3485
Transcriptomic and metabolomic profiling of long-lived growth hormone releasing hormone knock-out mice: evidence for altered mitochondrial function and amino acid metabolism
- 1 Department of Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- 2 Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA
- 3 The Jewish Hospital, Department of Internal Medicine, Cincinnati, OH 45236, USA
- 4 Targeted Metabolomics and Proteomics Laboratory; Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
received: November 8, 2019 ; accepted: January 27, 2020 ; published: February 23, 2020 ;https://doi.org/10.18632/aging.102822
How to Cite
Copyright © 2020 Hoffman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Numerous genetic manipulations that extend lifespan in mice have been discovered over the past two decades, the most robust of which has arguably been the down regulation of growth hormone (GH) signaling. However, while decreased GH signaling has been associated with improved health and lifespan, many of the underlying physiological changes and molecular mechanisms associated with GH signaling have yet to be elucidated. To this end, we have completed the first transcriptomic and metabolomic study on long-lived growth hormone releasing hormone knockout (GHRH-KO) and wild-type mice in brown adipose tissue (transcriptomics) and blood serum (metabolomics). We find that GHRH-KO mice have increased transcript levels of mitochondrial and amino acid genes with decreased levels of extracellular matrix genes. Concurrently, mitochondrial metabolites are differentially regulated in GHRH-KO. Furthermore, we find a strong signal of genotype-by-sex interactions, suggesting the sexes have differing physiological responses to GH deficiency. Overall, our results point towards a strong influence of mitochondrial metabolism in GHRH-KO mice which potentially is tightly intertwined with their extended lifespan phenotype.