By 2020, two-thirds of the global burden of disease will be attributable to chronic non-communicable diseases (e.g. cardiovascular disease and diabetes), most of them strongly associated with diet. The pandemic of these diseases is likely, at least in part, to be due to a mismatch between our current dietary patterns (i.e. excessive calories and fat intake coupled with reduced dietary fiber intake) and those during man’s early stages of evolution which our genes were programmed to respond to. However, the interactions between our diet, genetic factors and the development of these diseases are not fully understood.
Several microarray transcription profiling studies have examined the effects of a high-fat, calorie-dense (HFC) diet but reported contradictory findings. One possible reason for these discrepant findings may be due to the varying lengths of the feeding period. We hypothesized that the HFC diet would initially elicit compensatory interrelated responses between feeding behaviour and gene expression levels and that such compensatory responses might diminish over time with the continued intake of a HFC diet.
Therefore, we sequentially examined the effects of feeding a HFC diet to female C57BL/6J mice. These included examining the feeding behaviour and the transcriptomic profile of genes involved in the lipid metabolism in the liver and white adipose tissue over a period of 10 weeks, making measurements at weeks 2, 4 and 10. In parallel, we measured common phenotypic parameters associated with cardiovascular diseases and obesity (e.g. plasma lipid, leptin and insulin levels).
Our results suggested that the early responses to HFC feeding were possibly aimed at reducing food intake, down-regulating the mRNA levels of lipogenic hepatic genes and up-regulating the mRNA levels of genes involved in fatty acid oxidation. However, prolonged HFC feeding appeared to disrupt this adaptation, leading to increased food intake and marked increases in weight and body fat. Lipogenic genes were also up-regulated. These effects were clearly dependent on the duration of HFC feeding and became evident after 4 weeks. We have proposed a possible model linking leptin signalling, hepatic lipid metabolism and the control of food intake during the early and later stages of high-fat, calorie-dense feeding. Our sequential observations may help to explain some of the discrepant findings in previous studies.
There are only a few studies examining the relationship between dietary fiber and gene expression. These studies are limited to the gastrointestinal tract or only one or two hepatic genes. Therefore, in a separate experiment, the thesis also examined sequentially the effects of a high-fiber diet containing psyllium husk on the expression levels of genes involved in lipid metabolism, using microarray technology. Whilst plasma lipids were reduced by high-fiber feeding, mRNA levels of hepatic genes in cholesterol synthesis were up-regulated throughout the feeding period and lipogenic genes were also up-regulated with prolonged feeding.
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Sequential Effects of A High-Fat, Calorie-Dense Diet or A High-Fiber Diet
