The combined effects of dietary protein and fat intake during the promotion phase of 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats

A 3 X 3 factorial experiment was conducted to examine the effects of dietary protein (8, 16 or 32% of energy from casein) and dietary fat (12, 24 or 48% of energy from corn oil) on the promotion phase of 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis in rats. A purified diet with protein and fat supplying 16 and 24% of energy, respectively, was fed to 360 rats. After 4 wk each rat received DMBA (20 mg/kg) via gastric intubation. Forty rats were then randomly assigned to each of the nine dietary treatments for 28 wk. We observed no effects of protein or interactions between protein and fat on mammary tumorigenesis. At necropsy, rats fed diets containing 12, 24 and 48% of energy from corn oil following DMBA administration showed tumor prevalences of 53, 60 and 70% with 109, 127 and 140 total tumors, respectively. Linear logistic statistical modeling indicated that each doubling of dietary fat concentration multiplied the odds of finding a tumor of any histologic type at necropsy by 1.52. Dietary fat had no significant effects on the prevalence of adenomas or fibroadenomas, whereas those fed corn oil at 12, 24 and 48% of dietary energy showed adenocarcinoma prevalences of 34, 41 and 52% with total adenocarcinoma counts of 66, 75 and 96, respectively. Our results suggest that increasing dietary fat enhanced the promotion of DMBA-induced breast carcinogenesis over a wide range of protein intake.     

The combined effects of dietary protein and fat on 7,12-dimethylbenz(a)anthracene-induced breast cancer in rats

A 3 X 3 factorial experiment was conducted to examine how protein content (8, 16, 32% of kilocalories from casein) and fat content (12, 24, 48% of kilocalories from corn oil) interact to influence 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis in rats. Forty weanling Sprague-Dawley rats were assigned to each of 9 diets fed ad libitum. After 4 weeks each rat received DMBA (20 mg/kg) via gastric intubation. No substantial statistical interactions of protein and fat were observed on tumor incidence. Increasing dietary corn oil increased the percentage of rats with palpable tumors. Rats fed diets containing 12, 24 and 48% of kilocalories from corn oil showed 35, 49 and 70% tumor prevalence at necropsy, and the total number of tumors per fat level was 65, 81 and 182, respectively. Each doubling of dietary fat concentration approximately doubled the odds of a rat developing a tumor. Multiple tumors were more common with the highest corn oil intake. The odds of finding a second tumor in rats with one tumor increased by a factor of 7.5 when fat kilocalories were increased from 24 to 48% compared to a decrease of one-third when fat kilocalories were increased from 12 to 24%. Dietary corn oil significantly increased the prevalence of adenocarcinomas and adenomas but not fibroadenomas. Dietary protein did not significantly affect tumor prevalence. However, tumors palpated in rats fed 16% of kilocalories as protein regressed more frequently than in rats fed low or high protein diets. Multiple logistic-regression results indicate that, in addition to the response to dietary corn oil, tumorigenesis was increased in rats with greater ad libitum food consumption. This conclusion is supported by reanalysis that used direct rate adjustment and average partial association tests.     

Effects of daidzein, genistein, and 17beta-estradiol on 7,12-dimethylbenz[a]anthracene-induced mutagenicity and uterine dysplasia in ovariectomized rats

Phytoestrogens, primarily isoflavones daidzein (DZ) and genistein (GE), are increasingly used by postmenopausal women as an alternative to hormone replacement therapy due to reports that estrogen therapy increases the risk of breast and endometrial cancers. These compounds, as estrogen receptor agonists, may influence chemical carcinogenesis in estrogen-responsive tissues such as the uterus. We utilized ovariectomized (OVX) rats to model menopause and assessed the effects of dietary DZ, GE, or 17beta-estradiol (E2) on carcinogen-induced mutagenesis and carcinogenesis in the rat uterus. Big Blue transgenic rats (derived from Fischer 344 strain) were exposed to 7,12-dimethylbenz[a]anthracene (DMBA) in the presence or absence of the supplements. At 16- or 20-wk sacrifice, the uteri were removed and processed to determine mutant frequencies (MFs) and immunohistochemical or histopathological parameters, respectively. In rats treated with DMBA alone, a significant increase in lacI MFs (P < 0.01) in both OVX and intact (INT) rats was observed. The DMBA-induced MFs were not significantly altered by dietary DZ, GE, or E2 in both OVX and INT rats. Although dysplasia was not induced in the uterus of OVX and INT rats treated with DMBA alone, it was detected in 55% of OVX rats fed E2 alone and in 100% of OVX rats fed E2 along with DMBA exposure. Cell proliferation also was significantly higher in OVX rats fed E2 and treated with DMBA. In rats fed the isoflavones and treated with DMBA, the incidence of dysplasia was either reduced or virtually absent in both OVX and INT groups. These results indicate that a high incidence of dysplasia was associated with E2 feeding with or without DMBA treatment in the OVX rats, whereas the incidence was low in rats fed DZ or GE and treated with DMBA, suggesting a weak estrogen receptor agonist of DZ or GE in the rat uterus. The absence of dysplasia in OVX rats exposed to DMBA alone also suggests, in part, a promotional mechanism via estrogen- or isoflavone-driven cell proliferation.     

Protective effects of a mixture of dietary agents against 7,12-dimethylbenz[a]anthracene-induced genotoxicity and oxidative stress in mice

We investigated the effects of pretreatment with tomato, garlic, and turmeric, alone and in combination, against 7,12-dimethylbenz[a]anthracene (DMBA)-induced genetic damage and oxidative stress in male Swiss mice. Measurement of the incidence of bone marrow micronuclei as well as the extent of lipid peroxidation and the status of the antioxidants reduced glutathione, glutathione peroxidase, and glutathione-S-transferase in the liver and erythrocytes were used as biomarkers of chemoprotection. In DMBA-treated animals, increased frequency of bone marrow micronuclei was accompanied by enhanced lipid peroxidation and antioxidant depletion. Pretreatment with tomato, garlic, and turmeric alone and a combination of these agents significantly reduced the frequencies of DMBA-induced bone marrow micronuclei as well as the extent of lipid peroxidation. These changes may be mediated by the antioxidant-enhancing effects of the dietary agents. The results of the present study suggest that a diet containing even low levels of different naturally occurring compounds is effective in exerting antigenotoxic effects by inhibiting DMBA-induced oxidative stress.     

S-allylcysteine, a garlic constituent, inhibits 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

The effect of S-allylcysteine (SAC), a water-soluble garlic constituent, on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis was investigated in male Syrian hamstes. Forty hamsters were divided into 4 groups of 10 animals. The right buccal pouches of the animals in Group I were painted with a 0.5% solution of DMBA in liquid paraffin three times a week. The animals in Group II were painted with DMBA as in Group I and, in addition, received 200 mg/kg body wt p.o. SAC three times a week on days alternate to DMBA application. Group III animals received SAC as in Group II. Group IV animals received neither DMBA nor SAC and served as the control. The hamsters were killed after an experimental period of 14 wk. Measurement of lipid peroxidation, the antioxidant enzymes superoxide dismutase (SOD) and catalase, in the buccal pouch mucosa, liver, and circulation was used to monitor the chemopreventive potential of SAC. All hamsters painted with DMBA alone developed tumors identified histologically as well-differentiated squamous cell carcinomas. In hamsters bearing DMBA-induced buccal pouch tumors, diminished lipid peroxidation in the tumor tissue was accompanied by decreased activities of SOD and catalase, whereas in the liver and circulation, enhanced lipid peroxidation was associated with compromised antioxidant defenses. Administration of SAC suppressed the incidence of DMBA-induced HBP tumors as revealed by the absence of carcinomas. Histologically, only keratosis was observed. SAC modulated DMBA-induced decreased susceptibility of the HBP to lipid peroxidation while simultaneously enhancing SOD and catalase activities, whereas in the liver and circulation, SAC decreased the extent of lipid peroxidation and significantly enhanced antioxidant activities. We suggest that SAC exerts its chemopreventive effects by modulating lipid peroxidation and enhancing antioxidant activities in the target organ as well as in the liver and circulation.     

Inhibitory effects of estrogenic compounds, 4-nonylphenol and genistein,on 7,12-dimethylbenz[a]anthracene-induced ovarian carcinogenesis in rats

The modifying effects of dietary feeding of estrogenic compounds, 4-nonylphenol (4-NP) and genistein (GS), on 7,12-dimethylbenz[a]anthracene (DMBA)-induced ovarian carcinogenesis were investigated in female Sprague-Dawley rats. We also assessed the effects of test compounds on proliferating cell nuclear antigen (PCNA) index and the expression of estrogen receptor (ER)-alpha and -beta and androgen receptor (AR) in induced neoplasms. Rats were given a single injection of DMBA (0.01 ml of 0.5- DMBA suspended in olive oil) into their left ovary to induce ovarian neoplasms. They also received the experimental diet containing 25 to 250 ppm 4-NP or GS for 50 weeks, starting one week after the dosing of DMBA. DMBA exposure produced ovarian adenocarcinoma with an incidence of 35% at the end of the study (Week 51). Dietary administration of 4-NP or GS caused significant reduction in the incidence of ovarian adenocarcinoma: 86% reduction (P=0.0218) by feeding of 25 or 250 ppm 4-NP and 25 ppm GS, and 100% reduction (P=0.0042) by feeding of 250 ppm GS. The PCNA index in adenocarcinomas was higher than that of surface ovarian epithelium. ER-alpha, beta and AR were expressed in a variable percentage of moderately and poorly differentiated adenocarcinoma cell nuclei, but not in well-differentiated adenocarcinoma cells. These results might suggest that dietary feeding of estrogenic compounds either synthetic (4-NP) or natural (GS) could act as an inhibitor of DMBA-induced rat ovarian carcinogenesis.     

Dose-dependent protection by tomato against 7,12-dimethylbenz[a]anthracene-induced genotoxicity and oxidative stress in mice

This study was designed to investigate the protective role of pretreatment with graded doses of freshly prepared tomato paste against 7,12-dimethylbenz[a]anthracene (DMBA)-induced genetic damage and oxidative stress in male Swiss mice. The incidence of bone marrow micronuclei and the extent of hepatic lipid peroxidation and the antioxidants glutathione, glutathione peroxidase, and glutathione S-transferase were monitored. Three different concentrations (0.5, 1, and 2 g/kg body weight) of tomato paste were tested for their anticlastogenic effects against DMBA (35 mg/kg body weight). Increased frequency of micronuclei and enhanced lipid peroxidation accompanied by compromised antioxidant defenses were observed in DMBA-treated animals. Pretreatment with all three doses of tomato paste significantly reduced the frequencies of DMBA-induced micronuclei and oxidative stress. These findings demonstrate that administration of tomato paste protects against the clastogenic effects of DMBA by decreasing lipid peroxidation and enhancing the antioxidant status.     

Enhancement of erythrocyte antioxidants by green and black tea polyphenols during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

We evaluated the comparative chemopreventive efficacy of green tea polyphenols (polyphenon-E) and black tea polyphenols (polyphenon-B) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Lipid peroxidation, reduced and oxidized glutathione (GSH and GSSG, respectively), and the GSH-dependent enzymes glutathione peroxidase and glutathione S-transferase in the erythrocytes were used as biomarkers of chemoprevention. Enhanced lipid peroxidation in erythrocytes of DMBA-treated animals was accompanied by a significant decrease in the antioxidant status. Dietary administration of polyphenon-E and -B to DMBA-treated animals significantly decreased the extent of lipid peroxidation and enhanced the levels of GSH, GSH/GSSG ratio, and activities of GSH-dependent enzymes. Our study provides evidence that polyphenon-B is more effective in inhibiting HBP carcinogenesis than polyphenon-E by enhancing the antioxidant status, suggesting that polyphenon-B may have a major impact in the chemoprevention of oral cancer.     

Influence of prior dietary protein intake on metabolism, DNA binding and adduct formation of 7,12-dimethylbenz[a]anthracene in isolated rat mammary epithelial cells

These studies were designed to examine the influence of prior dietary protein intakes in rats on the ability of their isolated mammary cells to metabolize 7,12-dimethylbenz[a]anthracene (DMBA). Total metabolism of DMBA increased as dietary protein increased. After 6 h of incubation, water-soluble metabolites made only a minor (less than 12%) contribution to total DMBA metabolism. The binding of DMBA to isolated mammary cell DNA after 6 h of incubation from rats fed 15% dietary protein was 20% higher than binding from cells of rats fed 7.5% dietary protein. The increased binding in mammary epithelial cells from rats fed 15% protein was associated with an increase in the syn-dihydrodiol-epoxide adduct. The syn-dihydrodiol-epoxide:deoxyadenosine adduct was the major contributor to binding. The present studies are consistent with a decrease in carcinogen activation in tissues obtained from animals fed diets limiting in protein.     

Inhibition of 7,12-dimethylbenz[a]anthracene-induced lipid peroxidation and mammary tumor development in rats by vitamin E in conjunction with selenium.

The effects of combined dietary vitamin E supplementation and a relatively low increase in selenium levels on 7,12-dimethylbenz[a]anthracene (DMBA) induction of lipid peroxidation in the short term and development of mammary tumors in the long term were investigated in female Sprague-Dawley rats. Control animals were fed the basal diet (20 mg/kg vitamin E and 0.6 mg/kg selenium) throughout the experiment. Three other groups received a high vitamin E diet (235 mg/kg vitamin E and 0.6 mg/kg selenium) at different times, the first two from three weeks after DMBA treatment and the other throughout the experiment. When the vitamin E diet with selenium supplementation was applied until three weeks after DMBA or until the termination of the experiment, tumor yields (tumors per rat) were significantly inhibited compared with the control group. On the other hand, delaying the supplementation of vitamin E until three weeks postcarcinogen produced no prophylactic effect. The elevation of lipid peroxidation levels observed immediately after DMBA administration was also significantly inhibited in both mammary fat pads and livers of animals in the high vitamin E group. It was therefore concluded that the inhibitory effect of vitamin E in combination with selenium on tumorigenesis might be causally related to reduction of carcinogen treatment associated with lipid peroxidation, the latter presumably playing an important role in DMBA-induced mammary carcinogenesis.     

Milk inhibits the regression of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in ovariectomized rats

Epidemiological studies have yielded inconsistent results regarding the relation between the milk consumption and breast cancer risk. In this study, rats were induced mammary tumors by 7,12-dimethylbenz(a)anthracene. When tumors developed to acceptable levels, rats were placed into 1 of 3 treatment groups. Those in the negative control group and the milk group were ovariectomized, whereas those in the positive control group were sham operated. After grouping, tumor incidence remained 100%, and tumor number and volume increased in the positive control group. However, tumors in the 2 ovariectomized groups regressed. Compared with the negative control group, tumor incidence and tumor number and volume per rat in the milk group became significantly higher from Week 6 and Week 4, respectively. Insulin-like growth factor-I levels were borderline significantly higher in the milk group than in the negative control group at autopsy. Although plasma 17beta-estradiol levels did not differ significantly, estrogenicity was found in the milk group because uterine weight was significantly heavier in the milk group than in the negative control group. In conclusion, commercial milk inhibited the regression of carcinogen-induced mammary tumors in ovariectomized rats.     

Effects of dietary protein, fat and restriction on body composition and energy balance in lactating rats

Isoenergetic diets formulated at three levels of dietary protein using 12,24 and 40% casein and at two levels of fat using 2.26 and 13.82% corn oil were fed at five levels of intake, ad libitum, 75, 62.5, 50 and 37.5% of average ad libitum intake, to 90 lactating rats from d 7 to 14 of lactation. Regression equations developed from lactating rats killed on d 7 of lactation were used to calculate initial body composition and energy of rats killed on d 14 of lactation. Changes in body weight and body water were significantly (P less than 0.05) affected by dietary fat and protein, but change in dry lean body mass was affected only by level of dietary fat, whereas body nitrogen and fat and lean body energy were not affected by level of dietary fat or protein. However, restricted intake significantly increased loss of all these. Likewise, restricted intake decreased milk production. Changes in weights of heart and liver were not affected by diet or intake, whereas intestinal weight decreased with intake restriction. Liver enzyme activities were markedly affected by intake restriction, whereas responses to dietary protein and fat were marginal.     

Reduction in 7,12-dimethylbenz[a]anthracene-induced hepatic cytochrome-P450 1A1 expression following soy consumption in female rats is mediated by degradation of the aryl hydrocarbon receptor

Consumption of a soy diet has been found to reduce cancer incidence in animals and is associated with reduced cancer risk in humans. In this study, the effect of consuming soy protein isolate (SPI) on the aryl hydrocarbon receptor (AhR)-mediated signaling pathway was investigated. Female Sprague-Dawley rats were fed AIN-93G diets with (+) or without (-) SPI-bound phytochemicals or casein (CAS) protein and gavaged orally with 7,12-dimethylbenz[a]anthracene (DMBA) or sesame oil. We found reduced (P < 0.05) DMBA-induced hepatic cytochrome-P450 1A1 (CYP1A1) activity, apoprotein, and mRNA expression along with the reduced binding of AhR-AhR nuclear translocator complex to CYP1A1 gene promoter in SPI(+)-fed rats compared with CAS- or SPI(-)-fed rats. Basal AhR protein expression was lower (P < 0.05) in SPI(+)-fed rats compared with CAS- or SPI(-)-fed groups. AhR levels were reduced (P < 0.05) after rats were fed SPI(+) for >20 d. Experiments in which SPI(+)-fed rats were weaned to CAS diets demonstrated that AhR reduction by SPI(+) is not imprinted metabolically. To determine the molecular mechanisms of SPI(+)-mediated AhR reduction, an ex vivo model was developed using FGC-4 cells treated with serum from CAS- or SPI(+)-fed rats. SPI(+) serum treatment of FGC-4 cells reduced AhR expression and DMBA-induced CYP1A1 expression (P < 0.05). The reduction in AhR expression was in part due to the shorter half-life of AhR protein. Our findings suggest that the cancer preventive effect of soy-based diets is mediated in part by reduction in AhR protein level posttranslationally, which reduces procarcinogen-induced CYP1A1 induction and metabolic activation.     

Inhibitory effects of combination of lycopene and genistein on 7,12- dimethyl benz(a)anthracene-induced breast cancer in rats

Breast cancer is one of the most common cancers in women. Carotenoids and soy isoflavones have been postulated to have breast cancer preventive effects. We investigated the potential preventive effects of lycopene and genistein, alone and in combination, on breast cancer development in female Wistar rats treated with 7,12-dimethylbenz[a]anthracene (DMBA), a carcinogen known to induce breast tumors. Mammary carcinogenesis was initiated by a single, oral gavage of DMBA (80 mg/kg body weight) at 55 days of animal age. Fifty female Wistar rats were divided into 5 experimental groups having 10 animals per group: Group 1 (normal control), Group 2 (DMBA control), Group 3 (DMBA + lycopene), Group 4 (DMBA + genistein), and Group 5 (DMBA + lycopene and genistein). Rats were fed either lycopene (20 mg /kg bw) or genistein (2 mg /kg bw) by oral gavage (3 times per week) starting 2 wk prior to DMBA injection. Treatment was continued for 20 wk. Rats treated with DMBA developed mammary tumors with 100% tumor incidence during the 20-wk study. Inhibition of mammary cancer incidence by lycopene (70%), genistein (60%) and their combination (40%) was observed. Tumor weight decreased by 48%, 61%, and 67%, and mean tumor volume decreased by 18%, 35%, and 65% with lycopene, genistein, and lycopene + genistein, respectively (P < 0.01 for the combination). The proportions of adenocarcinoma masses decreased with lycopene and genistein combination (P < 0.05). Administration of lycopene and genistein combination suppressed breast cancer development and was associated with a decrease in MDA, 8-isoprostane, and 8-OhdG levels and with an increase in serum lycopene and genistein levels. Animals administered DMBA developed breast cancer, which was associated with increased expression of Bcl-2 and decreased expression of Bax, caspase 3, and caspase 9 in mammary tissues. Administration of genistein and lycopene in combination was more effective in inhibiting DMBA-induced breast tumors and modulating the expression of apoptosis associated proteins than the administration of each agent alone. Our results suggest that lycopene and genistein are potent antioxidants and, when given in combination, offer maximum protection against DMBA-induced mammary carcinogenesis.     

Lack of a significant effect of arctiin on development of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in ovariectomized Sprague-Dawley rats

Arctiin, a plant lignan, is metabolized to hormone-like compounds with weak estrogenic and antioxidative activity in experimental animals and man. To clarify its influence on mammary carcinogenesis, female rats were administrated 7,12-dimethylbenz(a)anthracene (DMBA) once, and when the incidence of palpable mammary tumors reached 50%, subjected to ovariectomy (OVX) and divided into tumor-bearing [DMBA-Tumor (+)] and no-tumor-bearing [DMBA-Tumor (-)] groups, subgroups of each then being fed soybean-free diet containing 0, 40, 200, and 1000 ppm of arctiin for 31 wk. The incidence and multiplicity of palpable tumors in the 200 ppm DMBA-Tumor (+) subgroup from week 12 of arctiin treatment tended to be decreased as compared to the 0 ppm subgroup and at terminal sacrifice, the volume of histopathologically defined mammary tumors was decreased in the 40 ppm DMBA-Tumor (-) subgroup, but again without statistical significance. In conclusion, weak inhibitory effects of arctiin on DMBA-induced mammary tumor development were suggested in OVX rats, but any further assessment is needed to obtain conclusive results.     

Fat intake and breast cancer risk in an area where fat intake is low: a case-control study in Indonesia

BACKGROUND: Associations of fat and other macronutrients with breast cancer risk are not clear in areas where fat intake is low. METHODS: We conducted a hospital-based case-control study from 1992 to 1995 in Jakarta, Indonesia. RESULTS: The study, based on 226 cases and 452 age and socioeconomic status matched controls, provided the following findings. (a) In the pre-marriage period, the greater the fat or protein consumption, the larger the risk, whereas decreasing risk with increasing carbohydrate intake was detected. The odds ratio (OR) for the highest quartile of intake relative to the lowest was 8.47 (95% CI: 4.03-17.8) for fat, 2.19 (95% CI: 1.30-3.69) for protein, and 0.16 (95% CI: 0.08-0.31) for carbohydrate. A positive association with fat and a negative one with carbohydrate were also observed for the post-marriage period, but of weaker magnitude compared to the pre-marriage period. (b) The effects of macronutrient intakes were stronger among premenopausal than among postmenopausal women. (c) Most of the associations of protein and carbohydrate were insignificant after adjustment for fat intake. CONCLUSIONS: These findings suggest that fat intake might be an important determinant of breast cancer among populations with a low fat diet in Indonesia.     

能量平衡状态下不同膳食脂肪摄入量对大鼠血脂、体脂、脂联素及瘦素的影响

目的探讨能量平衡状态下,不同膳食脂肪摄入量对大鼠血糖、血脂、体脂、胰岛素及瘦素的影响。方法 40只SD雄性大鼠随机分为4组,分别饲喂等能量低脂饲料(脂肪供能比5%)、普通饲料(脂肪供能比15%)、中脂饲料(脂肪供能比25%)和高脂饲料(脂肪供能比40%)。测量第0、5和10周血糖和血脂水平及第0、10周血清脂联素和瘦素水平。10周末取肾周及睾周脂肪垫,计算体脂比,用realtime PCR方法测算脂肪中脂联素及瘦素mRNA的相对表达水平。结果喂养5周及10周后,中脂组和高脂组大鼠血清中甘油三酯含量显著低于低脂组和普通组;10周末,中脂组脂肪中脂联素mRNA的表达水平显著低于低脂组;体脂比、血糖、血胆固醇、血清脂联素和瘦素水平以及脂肪中瘦素mRNA的相对表达水平,各组间均无显著性差异。结论能量平衡状态下,不同的膳食脂肪摄入量对大鼠体脂、血糖、血清甘油三酯、脂联素及瘦素水平均无影响。     

Impact of dietary fat content and fat oxidation on energy intake in humans

Three studies were performed to assess the effects of a high-fat diet and exercise-induced changes in fat oxidation on energy intake in humans. In the first study the short-term effect of a high-fat diet on spontaneous energy intake was investigated. The second study evaluated the long-term effect of a high-fat diet on adiposity and the third study evaluated the effect of exercise-induced changes in fat oxidation on short-term regulation of energy intake when subjects were consuming a high-fat diet. The results of these studies indicate that a high-fat diet induces a short-term hyperphagia, a high percentage of lipids in the usual diet is associated with a higher adiposity, and exercise may attenuate or amplify the high-fat, diet-induced hyperphagia, depending on the magnitude of the exercise-induced increase in fat oxidation.     

Estrogen deprivation and excess energy supply accelerate 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in C3H/HeN mice

BACKGROUND/OBJECTIVESObesity is a risk factor of breast cancer in postmenopausal women. Estrogen deprivation has been suggested to cause alteration of lipid metabolism thereby creating a cellular microenvironment favoring tumor growth. The aim of this study is to investigate the effects of estrogen depletion in combination with excess energy supply on breast tumor development.MATERIALS/METHODSOvariectomized (OVX) or sham-operated C3H/HeN mice at 4 wks were provided with either a normal diet or a high-fat diet (HD) for 16 weeks. Breast tumors were induced by administration of 7,12-dimethylbenz(a)anthracene once a week for six consecutive weeks.RESULTSStudy results showed higher serum concentrations of free fatty acids and insulin in the OVX+HD group compared to other groups. The average tumor volume was significantly larger in OVX+HD animals than in other groups. Expressions of mammary tumor insulin receptor and mammalian target of rapamycin proteins as well as the ratio of pAKT/AKT were significantly increased, while pAMPK/AMPK was decreased in OVX+HD animals compared to the sham-operated groups. Higher relative expression of liver fatty acid synthase mRNA was observed in OVX+HD mice compared with other groups.CONCLUSIONSThese results suggest that excess energy supply affects the accelerated mammary tumor growth in estrogen deprived mice.