Intermittent food restriction prevents mammary tumors

间歇性食物限制可预防乳腺肿瘤

• 批准号: 7368099
• 负责人: Margot P Cleary
• 金额: $ 23.33万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7368099
• 关键词: Animals; Apoptosis; Body Weight; Body Weight decreased; Caloric Restriction; Calories; Cell Proliferation; Chemopreventive Agent; Chronic; Development; Diet; Dietary Component; Dietary Intervention; Effectiveness of Interventions; Energy Intake; Epidemiologic Studies; Etiology; Fatty acid glycerol esters; Female; Gene Expression; Goals; Growth Factor; Health; Human; Incidence; Insulin-Like Growth Factor I; Insulin-Like-Growth Factor I Receptor; Intervention; Leptin; Mammary Neoplasms; Mammary gland; Mediating; Modeling; Mus; Nutrient; Obesity; Oncogenes; Outcome; Overweight; Postmenopause; Protocols documentation; Recording of previous events; Reporting; Risk; Rodent; Role; Serum; Signal Pathway; Signal Transduction; Surrogate Markers; Tissues; Transgenic Mice; Transgenic Organisms; Treatment Protocols; Tumor Burden; Weight; Woman; cancer risk; feeding; food restriction; insight; leptin receptor; malignant breast neoplasm; prevent; protective effect; receptor; response; tumor

DESCRIPTION (provided by applicant): Many attempts have been made to identify dietary components that prevent development of breast cancer and/or mammary tumors (MTs). Few studies have produced conclusive findings. However, chronic caloric restriction consistently lowers MT incidence and extends latency in rodents. We find that intermittent restriction/refeeding prevents MT development in transgenic MMTV-TGF-a mice to a greater degree than does chronic restriction, i.e., 3% vs 44% incidence (vs 77% for ad libitum-fed mice). Thus, the manner in which calories are restricted has a major impact on MT development. Hypotheses: 1- The protective effect of intermittent restriction/refeeding is mediated by decreased serum IGF-I and leptin and effects on signaling pathways and/or proliferation/apoptosis; 2-The protective effect of intermittent restriction/refeeding is dependent upon periods of moderately severe caloric restriction and is modified by caloric intake and/or nutrient composition during refeeding; 3- The protective effects of chronic restriction and intermittent restriction/refeeding are dependent upon tumor etiology. In Specific Aim 1 the effect of intermittent restriction/refeeding and chronic restriction on serum IGF-I and leptin in longitudinal and cross-sectional protocols will be assessed. In Specific Aim 2 the effect of intermittent restriction/refeeding and chronic restriction on apoptosis, proliferation, and gene expression of IGF-I and leptin and their receptors in mammary tissue and MTs will be determined. In Specific Aim 3 the effect of serum leptin levels on the protective response of intermittent restriction/refeeding regimen on MT development will be determined. Specific Aim 4 will determine if the protective effect of intermittent caloric restriction/refeeding is dependent upon the MT oncogene and/or background strain of the transgenic mouse. Our long-term objectives are to establish nutrition intervention strategies applicable to humans and/or to provide insights leading to the development of chemopreventive agents to mimic this protective effect.

描述（由申请人提供）：已经进行了许多尝试，以鉴定防止乳腺癌和/或乳腺肿瘤（MTS）发展的饮食成分。很少有研究产生结论性的发现。但是，慢性热量限制始终降低MT的发生率并扩大啮齿动物的潜伏期。我们发现，间歇性限制/重新审核可阻止转基因MMTV-TGF-A小鼠的MT发展，比慢性限制更大，即3％vs 44％的发病率（vs Adbitum-Fibum-Fibum-fed小鼠的发病率为77％）。因此，限制卡路里的方式对MT的发展产生了重大影响。假设：1-间歇性限制/再进程的保护作用是由血清IGF-I和瘦素降低以及对信号通路和/或增殖/凋亡的影响所介导的； 2-间歇性限制/补充的保护作用取决于中度严重的热量限制周期，并通过加速摄入量和/或养分组成在补充过程中修饰； 3-慢性限制和间歇性限制/补充的保护作用取决于肿瘤病因。在特定的目标1中，将评估间歇性限制/补充限制和慢性限制对纵向和横截面方案中血清IGF-I和瘦素的影响。在特定的目标2中，将确定IGF-I和瘦素的凋亡，增殖和基因表达的间歇性限制/重新限制和慢性限制的影响，并确定其在乳腺组织和MTS中的受体。在特定目标3中，将确定血清瘦素水平对间歇性限制/重喂养方案对MT发育的保护性反应的影响。特定的目标4将确定间歇性热量限制/补充的保护作用是否取决于转基因小鼠的MT癌基因和/或背景菌株。我们的长期目标是建立适用于人类的营养干预策略和/或提供见解，从而导致化学预防剂的发展以模仿这种保护作用。

项目成果

The influence of different calorie restriction protocols on serum pro-inflammatory cytokines, adipokines and IGF-I levels in female C57BL6 mice: short term and long term diet effects.

• DOI: 10.1016/j.mgene.2016.12.013
• 发表时间: 2017-06
• 期刊: Meta gene
• 影响因子: 0.7
• 作者: Dogan S;Ray A;Cleary MP
• 通讯作者: Cleary MP

Effect of chronic and intermittent calorie restriction on serum adiponectin and leptin and mammary tumorigenesis.

• DOI: 10.1158/1940-6207.capr-10-0140
• 发表时间: 2011-04
• 期刊: Cancer prevention research (Philadelphia, Pa.)
• 作者: Rogozina OP;Bonorden MJ;Seppanen CN;Grande JP;Cleary MP
• 通讯作者: Cleary MP

Effects of leptin on the viability of MCF-7 and T47D cells at different glucose concentrations.

不同葡萄糖浓度下瘦素对 MCF-7 和 T47D 细胞活力的影响。

• 发表时间: 2020
• 期刊: Journal of experimental and clinical medicine
• 作者: Demirel,PinarB;Dogan,Soner;Ozorhan,Umit;Tuna,BilgeG;Schuster,ToddF;Cleary,MargotP
• 通讯作者: Cleary,MargotP

The balance between leptin and adiponectin in the control of carcinogenesis - focus on mammary tumorigenesis.

• DOI: 10.1016/j.biochi.2012.06.013
• 发表时间: 2012-10
• 期刊: BIOCHIMIE
• 影响因子: 3.9
• 作者: Grossmann, Michael E.;Cleary, Margot R.
• 通讯作者: Cleary, Margot R.

The protective effect of intermittent calorie restriction on mammary tumorigenesis is not compromised by consumption of a high fat diet during refeeding.

间歇性热量限制对乳腺肿瘤发生的保护作用不会因重新喂养期间高脂肪饮食的消耗而受到损害。

• DOI: 10.1007/s10549-013-2464-7
• 发表时间: 2013
• 期刊: Breast cancer research and treatment
• 影响因子: 3.8
• 作者: Rogozina,OlgaP;Nkhata,KataiJ;Nagle,EmilyJ;Grande,JosephP;Cleary,MargotP
• 通讯作者: Cleary,MargotP