Caloric restriction (CR) has been shown to inhibit carcinogenesis in both chemically induced and spontaneous rodent tumor models. Caloric restriction leads to a decrease in body fat, and obesity is a well-known risk factor for cancer. Given this relationship (CR leads to a reduction in fat and CR is associated with an inhibition of carcinogenesis), one might speculate that body fat is directly linked with cancer; however, the role of body fat in cancer progression and prevention is controversial. The proposed study will determine the role of body fat mass on cancer progression in a transgenic mouse mode of prostate cancer. Using a fixed food intake paradigm, we will manipulate body fat by altering energy expenditure between control and experimental animals. State-of-the-art methods (dual-energy X-ray absorptiometry and peripheral quantitative computed tomography) will be used to non-invasively and Iongitudinally measure body fat and body fat distribution. Energy expenditure, and, hence, body fat mass, will be manipulated using ambient temperature. Control animals will be housed at 35xC (a temperature within their thermoneutral zone), and the experimental group will be maintained at 24xC (a condition in which energy must be expended to maintain body temperature). The increased thermoregulatory cost, coupled with a fixed energy intake, will result in a lesser amount of body fat in the experimental group relative to control animals. If the cancer preventative effect of CR is due to a reduction in energy intake, there should be no difference in tumor incidence between control and experimental mice, since food intake is held constant. In contrast, if body fat is the mechanism through which CR works, then the experimental animals (housed at 24oC) should show a decreased incidence of prostate tumors relative to controls (housed at 35oC) due to a lesser amount of body fat. This study will provide evidence for the hypothesis that body fat is the pathway through which CR exerts its cancer protective effects in rodent tumor models.
| Huffman, Derek M; Grizzle, William E; Bamman, Marcas M et al. (2007) SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Res 67:6612-8 |
| Huffman, Derek M; Johnson, Maria S; Watts, Amanda et al. (2007) Cancer progression in the transgenic adenocarcinoma of mouse prostate mouse is related to energy balance, body mass, and body composition, but not food intake. Cancer Res 67:417-24 |
