Segment of rat chromosome 20 regulates diet-induced augmentations in adiposity, glucose intolerance, and blood pressure.
Previous linkage and association studies have suggested that a region of human chromosome 6 containing the tumor necrosis factor (TNF)-alpha gene is involved in the pathogenesis of obesity and obesity-associated hypertension. The aim of the present investigation was to establish whether a segment of rat chromosome 20 (RNO20), which also contains the TNF-alpha gene, determines diet-induced changes in adiposity and blood pressure (BP). The results showed that a transfer of the RNO20 segment from the normotensive Brown Norway (BN) rat onto the background of the spontaneously hypertensive rat (SHR) is associated with a significantly greater increase in adiposity, glucose intolerance, circulating leptin levels, and BP during 12-week, high-fat-diet feeding. In contrast, the transfer is not associated with significant changes in these variables during 12-week, normal-diet feeding. In addition, sequencing of the TNF-alpha gene revealed differences between SHR and BN in the 5'- and 3'-regulatory regions of the gene. Subsequent analyses of TNF-alpha gene expression in fat, muscle, and liver, however, did not provide support for the functional involvement of these differences. In summary, the investigated RNO20 segment contains 1 or more gene variants that affect adiposity, glucose tolerance, serum leptin levels, and BP, but only when the animals are exposed to a particular environment, ie, high-fat-diet feeding. Further studies are needed to identify genes mediating these effects. Considering current changes in our lifestyle involving an increased calorie and fat intake, we believe that gene-environment interactions, such as those described here, play an important role in the current epidemic of obesity and obesity-associated hypertension.
Pausova
Zdenka
Z
Laboratory of Functional Genomics, Centre de recherche, CHUM Hôtel-Die, 3850 St Urbain St, Montréal, Québec H2W 1T7, Canada. zdenka.pausova@umontreal.ca
Sedova
Lucie
L
Berube
Julie
J
Hamet
Pavel
P
Tremblay
Johanne
J
Dumont
Marc
M
Gaudet
Daniel
D
Pravenec
Michal
M
Kren
Vladimir
V
Kunes
Jaroslav
J
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002875:Chromosomes / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage*; D004822:Epididymis / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes / Q000235:genetics; D018149:Glucose Intolerance / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018482:Muscle, Skeletal / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D012187:Retroperitoneal Space; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
D004041:Dietary Fats; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha