Cited by 141Genetics, Aging, and Longevity in Model OrganismsAdipose Tissue and MetabolismMitochondrial Function and Pathology

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Mitochondrial gene expression and increased oxidative metabolism: Role in increased lifespan of fat-specific insulin receptor knock-out mice

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Katic, Masa, Kennedy, Adam R., Leykin, Igor, Norris, Andrew, McGettrick, Aileen, Gesta, Stephane, Russell, Steven J., Bluher, Matthias, Maratos‐Flier, Eleftheria, Kahn, C. Ronald·2007·Aging Cell

DOI 10.1111/j.1474-9726.2007.00346.xPMC PMC5715809

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Abstract

Caloric restriction, leanness and decreased activity of insulin/insulin-like growth factor 1 (IGF-1) receptor signaling are associated with increased longevity in a wide range of organisms from Caenorhabditis elegans to humans. Fat-specific insulin receptor knock-out (FIRKO) mice represent an interesting dichotomy, with leanness and increased lifespan, despite normal or increased food intake. To determine the mechanisms by which a lack of insulin signaling in adipose tissue might exert this effect, we performed physiological and gene expression studies in FIRKO and control mice as they aged. At the whole body level, FIRKO mice demonstrated an increase in basal metabolic rate and respiratory exchange ratio. Analysis of gene expression in white adipose tissue (WAT) of FIRKO mice from 6 to 36 months of age revealed persistently high expression of the nuclear-encoded mitochondrial genes involved in glycolysis, tricarboxylic acid cycle, beta-oxidation and oxidative phosphorylation as compared to expression of the same genes in WAT from controls that showed a tendency to decline in expression with age. These changes in gene expression were correlated with increased cytochrome c and cytochrome c oxidase subunit IV at the protein level, increased citrate synthase activity, increased expression of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) and PGC-1beta, and an increase in mitochondrial DNA in WAT of FIRKO mice. Together, these data suggest that maintenance of mitochondrial activity and metabolic rates in adipose tissue may be important contributors to the increased lifespan of the FIRKO mouse.

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Authors: Katic, M., Kennedy, A. R., Leykin, I., Norris, A., McGettrick, A., Gesta, S., Russell, S. J., Bluher, M., Maratos‐Flier, E., & Kahn, C. R.
Affiliations: Beth Israel Deaconess Medical Center (US)
Joslin Diabetes Center (US)
University of Iowa (US)
Corresponding author: Kahn, C. Ronald
ORCID: Norris, Andrew
Russell, Steven J.
Kahn, C. Ronald
Venue: Aging Cell
Publisher: Wiley
Published: 2007-09-24
Volume: 6
Issue: 6
Pages: 827-839
ISSN: 1474-9718 (ISSN-L)
1474-9726
DOI: 10.1111/j.1474-9726.2007.00346.x
PMC: PMC5715809
OpenAlex: W1960692735
Cited by: 141
References: 73
Citations by year: 2026: 3 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 10 · 2020: 9 · 2019: 4 · 2018: 2 · 2017: 10 · 2016: 5 · 2015: 14 · 2014: 7 · 2013: 9 · 2012: 11
FWCI: 2.69
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Aging Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (5r01dk069983-05, DK31036)
National Institute of Diabetes and Digestive and Kidney Diseases (R37DK031036, R01DK031036, R01DK056113, DK31036, P01DK056116, R01-DK-069983, DK-60837, R01DK060837)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords: lifespan extension, mitochondrial gene expression, oxidative metabolism, white adipose tissue, insulin signaling, caloric restriction, aging, PGC-1α, PGC-1β, mitochondrial DNA, cytochrome c, citrate synthase, respiratory exchange ratio, basal metabolic rate, leanness
MeSH terms: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Citrate (si)-Synthase, Citric Acid Cycle, Electron Transport Complex IV, DNA, Mitochondrial, Electron Transport, Glycolysis, Longevity, Mitochondria, Oxidation-Reduction, Receptor, Insulin, Thinness, Transcription Factors, Trans-Activators, Gene Expression, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Cytochromes c, Genes, Mitochondrial, Mice, Adipose Tissue, White

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Mitochondrial gene expression and increased oxidative metabolism: Role in increased lifespan of fat-specific insulin receptor knock-out mice

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