Effect of high fat diet on body weight and mammary tumor latency in MMTV-TGF-alpha mice.

OBJECTIVE The role of high fat diets in breast cancer/mammary tumor (MT) development is controversial. This may be partially attributable to variable effects of high fat diets on body weight. Here, we used a moderately high fat diet (32.5% fat calories) expected to cause obesity in most mice, but predicted to result in some mice remaining in the weight range of mice fed the low fat diet (11% fat calories). This provided the opportunity to compare mice fed the high fat diet exhibiting different body weights and mice of similar weight consuming high vs low fat diets. EXPERIMENTAL METHODS Transgenic MMTV-TGF-alpha mice, a model of postmenopausal breast cancer, consumed a low fat diet, that is, chow-fed (n=25) or a moderately high fat diet from 10 weeks of age (n=51). Body weight at 34 weeks of age was used to assign high fat diet mice to obesity-prone>overweight>obesity-resistant groups (n=17) (P<0.0001). Mice were euthanized when MTs developed or at 85 weeks of age. RESULTS Final body weights were highest in obesity-prone>overweight >obesity-resistant=chow-fed mice. Fat pads and fat pad:carcass were heaviest in obesity-prone followed by overweight mice. However, obesity-resistant mice had fat pad weights and fat pad:carcass three-fold greater than chow-fed mice. All groups had MT incidences between 72 and 82%. Obesity-prone mice exhibited the shortest MT latency (P<0.0001), but obesity-resistant mice had significantly shorter latency than chow-fed mice. CONCLUSIONS Consumption of a high fat diet increased adiposity and shortened MT latency in relation to its effect on body weight. These results indicate a complex role of dietary fat level on mammary tumorigenesis.