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

Masa Katic; Adam R. Kennedy; Igor Leykin; Andrew Norris; Aileen McGettrick; Stephane Gesta; Steven J. Russell; Matthias Bluher; Eleftheria Maratos-Flier; C. Ronald Kahn

doi:10.1111/j.1474-9726.2007.00346.x

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

Journal article

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

Masa Katic, Adam R. Kennedy, Igor Leykin, Andrew Norris, Aileen McGettrick, Stephane Gesta, Steven J. Russell, Matthias Bluher, Eleftheria Maratos-Flier and C. Ronald Kahn

Aging cell, Vol.6(6), pp.827-839

12/01/2007

DOI: 10.1111/j.1474-9726.2007.00346.x

PMCID: PMC5715809

PMID: 18001293

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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, β-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 γ coactivator 1α (PGC-1α) and PGC-1β, 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.

calorie restriction

diabetes

insulin resistance

mitochondria

obesity

PGC-1α

Details

Title: Subtitle: Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice
Creators: Masa Katic - Joslin Diabetes Center
Adam R. Kennedy - Beth Israel Deaconess Medical Center
Igor Leykin - Joslin Diabetes Center
Andrew Norris - University of Iowa
Aileen McGettrick - Joslin Diabetes Center
Stephane Gesta - Joslin Diabetes Center
Steven J. Russell - Joslin Diabetes Center
Matthias Bluher - Leipzig University
Eleftheria Maratos-Flier - Beth Israel Deaconess Medical Center
C. Ronald Kahn - Joslin Diabetes Center
Resource Type: Journal article
Publication Details: Aging cell, Vol.6(6), pp.827-839
DOI: 10.1111/j.1474-9726.2007.00346.x
PMID: 18001293
PMCID: PMC5715809
ISSN: 1474-9718
eISSN: 1474-9726
Language: English
Date published: 12/01/2007
Academic Unit: Endocrinology and Diabetes; Stead Family Department of Pediatrics; Biochemistry and Molecular Biology
Record Identifier: 9984288723902771

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