The Tnfα-Gene Locus and Body-Weight Response to a High-Fat Diet in Spontaneously Hypertensive Rats
Objective: Using linkage and association analysis, we have previously demonstrated that the TNFα−gene locus contributes to the determination of obesity and obesity-associated hypertension in hypertensive pedigrees of French-Canadian origin. The aim of the present study was to investigate whether the TNFα-gene locus is involved in the regulation of body weight (BW) response to a high-fat (HF) diet in spontaneously hypertensive rats (SHR). Methods: The effect of the TNFα−gene locus was investigated with the use of a congenic strain, SHR.1N, which differs from SHR by a segment of chromosome 20 originating from the normotensive Brown Norway rat and containing the TNFα gene. Sixteen-week-old SHR and SHR.1N were placed on either a normal (N; 5P14, Prolab 2500) or HF (F3282, Bio-Serv) diet for 12 weeks. BW was measured weekly. The BW response to the dietary intervention was assessed by three-way ANOVA with Strain (SHR and SHR.1N), Diet(N and HF) and Time (11 time points) as the main factors. Results: During the 12-week period, SHR (n = 16) and SHR.1N (n = 17) fed the HF diet increased their BW by 31% and 42%, respectively; and SHR (n = 13) and SHR.1N (n = 13) fed the N diet augmented their BW by only 18% and 19%, respectively. ANOVA demonstrated a significant effect of all three main factors, Strain (F1,55 = 6.86, p = 0.01), Diet (F1,55 = 85.69, p = 0.0001), and Time (F10,550 = 236.12, p = 0.0001), and a significant three-way interaction between Strain, Diet and Time (F10,550= 2.58, p = 0.04). Subsequent two-way ANOVA showed that the effect of Strain and Time-Strain interaction was significant in rats fed the HF diet (F1,31 = 11.01, p = 0.002; F10,310 = 6.7, p = 0.0001, respectively), but not in rats fed the N diet (F1,24 = 0.06, p = 0.8; F10,240 = 1.31, p = 0.3, respectively). Summary and Conclusion: During feeding with the HF diet, both SHR and SHR.1N increased their BW, but the increase was greater in SHR.1N. These results suggest that a gene(s) exist(s) within the differential chromosomal segment of SHR.1N, which is involved in regulation of the BW response to the HF diet. Considering the known functional properties of TNFα, the TNFα gene is the best candidate within the segment.