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(Hypertension. 2003;41:1047.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Segment of Rat Chromosome 20 Regulates Diet-Induced Augmentations in Adiposity, Glucose Intolerance, and Blood Pressure

Zdenka Pausova; Lucie Sedova; Julie Berube; Pavel Hamet; Johanne Tremblay; Marc Dumont; Daniel Gaudet; Michal Pravenec; Vladimir Kren; Jaroslav Kunes

From the Centre de recherche, Centre hospitalier de l’Université de Montréal (Z.P., L.S., J.B., P.H., J.T., M.D., D.G.), Montréal, Canada; and Charles University (M.P., V.K.) and the Institute of Physiology, Academy of Sciences (M.P., V.K., J.K.), Prague, Czech Republic.

Correspondence to Zdenka Pausova, Laboratory of Functional Genomics, Centre de recherche, CHUM Hôtel-Die, 3850 St Urbain St, Montréal, Québec H2W 1T7, Canada. E-mail zdenka.pausova{at}umontreal.ca

Previous linkage and association studies have suggested that a region of human chromosome 6 containing the tumor necrosis factor (TNF)- 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- 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- gene revealed differences between SHR and BN in the 5'- and 3'-regulatory regions of the gene. Subsequent analyses of TNF- 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.

Key Words: hypertension, obesity • diet • genetics • glucose • tumor necrosis factor • gene-environment interaction

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