Segment of rat chromosome 20 regulates diet-induced augmentations in adiposity, glucose intolerance, and blood pressure.

Abstract

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.

• Authors: Zdenka Pausova, Lucie Sedova, Julie Berube, Pavel Hamet, Johanne Tremblay, Marc Dumont, Daniel Gaudet, Michal Pravenec, Vladimir Kren, Jaroslav Kunes
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 41 Issue 5 Pg. 1047-55 (May 2003) ISSN: 1524-4563 [Electronic] United States
• PMID: 12654711 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• RNA, Messenger
• Tumor Necrosis Factor-alpha

Topics

• Adipose Tissue (drug effects, metabolism)
• Animals
• Blood Pressure (drug effects, physiology)
• Chromosomes (genetics)
• Dietary Fats (administration & dosage)
• Epididymis (metabolism)
• Gene Expression Regulation (drug effects)
• Genes (genetics)
• Glucose Intolerance (physiopathology)
• Heart Rate (drug effects)
• Liver (metabolism)
• Male
• Motor Activity (drug effects)
• Muscle, Skeletal (metabolism)
• RNA, Messenger (drug effects, genetics, metabolism)
• Rats
• Rats, Inbred BN
• Rats, Inbred SHR
• Retroperitoneal Space
• Sequence Analysis, DNA
• Time Factors
• Tumor Necrosis Factor-alpha (genetics, physiology)