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Systems genetics: elucidating networks that underlie heritable variation in adipose function
Author(s) -
Voy Brynn,
Nakata Chiaki,
Malm Ian,
Kalupahaishan,
MoustaidMoussa Naima,
Chesler Elissa,
Webb Lisa
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1353
Subject(s) - adipokine , adipose tissue , biology , leptin , adiponectin , genetics , population , genetic variation , endocrinology , obesity , gene , medicine , insulin resistance , environmental health
Excess adipose tissue not only physically stresses the organism but also disrupts homeostasis through release of adipokines. Our long term goal is to determine how heritable differences in adipose function impact risk for obesity and its consequences. We employ systems genetics, anchoring phenotypic variation to naturally occurring genetic polymorphisms in two mouse genetic reference populations (GRP): recombinant inbred BXD (C57BL/6J X DBA/2J) strains, and a panel of eight genetically diverse strains that are progenitors for the collaborative cross (CC), an emergent GRP. Body and fat pad weights, plasma hormone profiles and expression of adipokine genes were measured in males of 24 BXD strains and in both sexes of the CC parental strains. Our current progress demonstrates: adiposity is highly correlated with expression of some adipokines (e.g., leptin, r 2 = 0.628; p=0.00001), but not others (e.g., visfatin, r 2 =0.0109, p=0.944); a subset of tightly intercorrelated adipokines are regulated independent of adiposity; and sexually dimorphic relationships exist among adipokines and adipose mass. Ongoing assay of adiposity in emerging generations of CC mice confirms that this new GRP will provide physiological diversity reflective of its genetic diversity and on par with that in a human population, highlighting its utility as a tool to dissect the molecular factors that control adipose function.