QTLs influencing IGF-1 levels in a LOU/CxFischer 344F2 rat population. Tracks towards the metabolic theory of Ageing.
Growth Hormone & IGF Research. 2013-12-01; 23(6): 220-228
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1. Growth Horm IGF Res. 2013 Dec;23(6):220-8. doi: 10.1016/j.ghir.2013.08.002. Epub
2013 Aug 19.
QTLs influencing IGF-1 levels in a LOU/CxFischer 344F2 rat population. Tracks
towards the metabolic theory of Ageing.
Marissal-Arvy N(1), Duron E, Parmentier F, Zizzari P, Mormède P, Epelbaum J.
(1)INRA, Laboratory of Nutrition and Integrative Neurobiology, UMR1286, 33076
Bordeaux Cedex, France; Univ. Bordeaux, Laboratory of Nutrition and Integrative
Neurobiology, UMR1286, 33076 Bordeaux Cedex, France.
OBJECTIVE: Since a reduction of the insulin/IGF-1 signaling cascade extends life
span in many species and IGF-1 signaling might partly mediate the effects of
caloric restriction (CR), an experimental intervention for increasing longevity,
the purpose of the present study was to use quantitative trait loci (QTL)
analysis, an unbiased genetic approach, to identify particular regions of the
genome influencing plasma IGF-1 levels in an F2 intercross between F344 and LOU/C
rats; the latter being an inbred strain of Wistar origin, considered as a model
of healthy aging since it resists to age (and diet)-induced obesity.
DESIGN: F1 hybrids were obtained by crossbreeding LOU/C with F344 rats, and then
F1 were bred inter se to obtain the F2 population, of which 93 males and 94
females were studied. Total plasma IGF-1 levels were determined by
radioimmunoassay. A genome scan of the F2 population was made with 100
microsatellite markers) selected for their polymorphism between LOU/C and F344
strains (and by covering evenly the whole genome.
RESULTS: By simple interval mapping sex-dependent QTLs were found on chromosome
17 in males and on chromosome 18 in females. By multiple interval mapping,
additional QTLs were found on chromosomes 1, 4, 5, 6, 12, 15 and 19 in males and
on chromosomes 3, 5, 6, 12 and 17 in females. Only the markers D1Rat196 and
D12Mgh5 were found in both males and females. The majority of QTLs corresponded
to metabolic syndrome (cardiac function: n = 45 (30%), obesity/diabetes: n = 22
(15%), inflammation: n = 19 (13%) and only a limited number to body weight: n =
13 (9%), proliferation (n = 10 (7%) or ossification: n = 7 (5%). Ninety-six
candidate genes were located on the different QTLs. A significant proportion of
these genes are connected to IGF-1 production and receptor pathways (n = 18) or
metabolic syndrome (n = 11).
CONCLUSIONS: Subsequent studies are necessary to determine whether the genetic
networks underscored are also involved in age-associated obesity, diabetes and
inflammation as well as cardiovascular impairments.
© 2013. Published by Elsevier Ltd on behalf of Growth Hormone Research Society.
All rights reserved.
PMID: 24028904 [Indexed for MEDLINE]