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Distinct effects of calorie restriction and exercise on mammary gland gene expression in C57BL/6 mice.

ABSTRACT: Energy balance, including diet, weight, adiposity, and physical activity, is associated with carcinogenesis. Epidemiologic studies indicate that obesity and sedentary and/or active behavior are risk factors for breast cancer in postmenopausal women and survival in both premenopausal and postmenopausal breast cancer patients. Thus, understanding the influence of energy balance modulation on changes in gene expression patterns in the normal mammary gland is important for understanding mechanisms linking energy balance and breast cancer. In a 6-week-long study, female C57BL/6 mice (9-week-old) were randomized into four groups: (a) food consumed ad libitum (AL), (b) AL with access to running wheels (AL+EX), (c) 30% calorie restricted (CR), and (d) 30% CR with access to running wheels (CR+EX). CR mice received 70% of calories but 100% of all other nutrients compared with AL mice. Diet and exercise treatments, individually and combined, had significant effects on body composition and physical activity. Affymetrix oligomicroarrays were used to explore changes in gene expression patterns in total RNA samples from excised whole mammary glands. Contrasting AL versus CR resulted in 425 statistically significant expression changes, whereas AL versus AL+EX resulted in 45 changes, with only 3 changes included among the same genes, indicating that CR and EX differentially influence expression patterns in noncancerous mammary tissue. Differential expression was observed in genes related to breast cancer stem cells, the epithelial-mesenchymal transition, and the growth and survival of breast cancer cells. Thus, CR and EX seem to exert their effects on mammary carcinogenesis through distinct pathways.

SUBMITTER: Padovani M

PROVIDER: S-EPMC2798590 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Distinct effects of calorie restriction and exercise on mammary gland gene expression in C57BL/6 mice.

Padovani Michela M Lavigne Jackie A JA Chandramouli Gadisetti V R GV Perkins Susan N SN Barrett J Carl JC Hursting Stephen D SD Bennett L Michelle LM Berrigan David D

Cancer prevention research (Philadelphia, Pa.) 20091201 12

Energy balance, including diet, weight, adiposity, and physical activity, is associated with carcinogenesis. Epidemiologic studies indicate that obesity and sedentary and/or active behavior are risk factors for breast cancer in postmenopausal women and survival in both premenopausal and postmenopausal breast cancer patients. Thus, understanding the influence of energy balance modulation on changes in gene expression patterns in the normal mammary gland is important for understanding mechanisms l ...[more]

PMID: 19952363

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Project description:BackgroundObesity associates with low-grade inflammation and adipose tissue remodeling. Using sensitive high-throughput protein arrays we here investigated adipose tissue cytokine and angiogenesis-related protein profiles from obese and lean mice, and in particular, the influence of calorie restriction (CR).MethodsTissue samples from visceral fat were harvested from obese mice fed with a high-fat diet (60% of energy), lean controls receiving low-fat control diet as well as from obese and lean mice kept under CR (energy intake 70% of ad libitum intake) for 50 days. Protein profiles were analyzed using mouse cytokine and angiogenesis protein array kits.ResultsIn obese and lean mice, CR was associated with 11.3% and 15.6% reductions in body weight, as well as with 4.0% and 4.6% reductions in body fat percentage, respectively. Obesity induced adipose tissue cytokine expressions, the most highly upregulated cytokines being IL-1ra, IL-2, IL-16, MCP-1, MIG, RANTES, C5a, sICAM-1 and TIMP-1. CR increased sICAM-1 and TIMP-1 expression both in obese and lean mice. Overall, CR showed distinct effects on cytokine expressions; in obese mice CR largely decreased but in lean mice increased adipose tissue cytokine expressions. Obesity was also associated with increased expressions of angiogenesis-related proteins, in particular, angiogenin, endoglin, endostatin, endothelin-1, IGFBP-3, leptin, MMP-3, PAI-1, TIMP-4, CXCL16, platelet factor 4, DPPIV and coagulation factor III. CR increased endoglin, endostatin and platelet factor 4 expressions, and decreased IGFBP-3, NOV, MMP-9, CXCL16 and osteopontin expressions both in obese and lean mice. Interestingly, in obese mice, CR decreased leptin and TIMP-4 expressions, whereas in lean mice their expressions were increased. CR decreased MMP-3 and PAI-1 only in obese mice, whereas CR decreased FGF acidic, FGF basic and coagulation factor III, and increased angiogenin and DPPIV expression only in lean mice.ConclusionsCR exerts distinct effects on adipocyte cytokine and angiogenesis profiles in obese and lean mice. Our study also underscores the importance of angiogenesis-related proteins and cytokines in adipose tissue remodeling and development of obesity.

Dataset Information

Distinct effects of calorie restriction and exercise on mammary gland gene expression in C57BL/6 mice.

Publications

Distinct effects of calorie restriction and exercise on mammary gland gene expression in C57BL/6 mice.

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