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

Effect of chronic and intermittent calorie restriction on serum adiponectin and leptin and mammary tumorigenesis.
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DOI:
10.1158/1940-6207.capr-10-0140
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发表时间:
2011-04
期刊:
Cancer prevention research (Philadelphia, Pa.)
影响因子:
--
通讯作者:
Cleary MP
Cleary MP
中科院分区:
其他
文献类型:
--
作者:
Rogozina OP;Bonorden MJ;Seppanen CN;Grande JP;Cleary MP

文献摘要

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研究了慢性(CCR)和间歇性(ICR)热量限制对血清脂联素和瘦素水平与乳腺肿瘤发生的关系。10-将5周龄MMTV-TGF-α雌性小鼠分配至自由采食(AL)(AIN-93 M饮食)、ICR(3周50%热量限制,AIN-93 M-mod饮食,2倍蛋白质、脂肪、维生素和矿物质,随后3周100%AL消耗AIN-93 M)和CCR(每个6周ICR周期匹配的热量和营养摄入,AL的约75%)组。在79周龄(限制结束)或82周龄(再喂养结束)处死小鼠。在周期1、3、5、8、11和终末采集血清。AL、CCR和ICR小鼠的乳腺肿瘤发生率分别为71.0%、35.4%和9.1%。各组间血清脂联素水平相似,CCR或ICR均无影响。AL小鼠血清瘦素水平随日龄增加而升高,但长期CCR和ICR可显著降低血清瘦素水平。ICR方案也与脂联素:瘦素比值升高相关。此外,与AL小鼠相比,ICR限制小鼠乳腺组织AdipoR 1表达增加,瘦素和ObRb表达减少。无瘤ICR小鼠的乳腺脂肪垫脂联素表达高于AL和CCR小鼠,而所有荷瘤小鼠的乳腺脂肪垫脂联素信号均较弱。虽然我们没有证明脂联素或瘦素与个体小鼠乳腺肿瘤发生有关,但我们确实发现血清瘦素降低和脂联素:瘦素比值升高与间歇性热量限制的保护作用有关。
The effect of chronic (CCR) and intermittent (ICR) caloric restriction on serum adiponectin and leptin levels was investigated in relation to mammary tumorigenesis. 10-wks old MMTV-TGF-α female mice were assigned to ad libitum-fed (AL) (AIN-93M diet), ICR (3-wks 50% caloric restriction, AIN-93M–mod diet, 2x protein, fat, vitamins, and minerals followed by 3-wks 100% AL consumption of AIN-93M), and CCR (calorie and nutrient intake matched for each 6-wks ICR cycle, ∼75% of AL) groups. Mice were sacrificed at 79 (end of restriction) or 82 (end of refeeding) wks of age. Serum was obtained in cycles 1, 3, 5, 8, 11 and terminal. Mammary tumor incidence was 71.0%, 35.4%, and 9.1% for AL, CCR and ICR mice, respectively. Serum adiponectin levels were similar among groups with no impact of either CCR or ICR. Serum leptin level rose in AL mice with increasing age but was significantly reduced by long-term CCR and ICR. The ICR protocol was also associated with an elevated adiponectin:leptin ratio. In addition, ICR-Restricted mice had increased mammary tissue AdipoR1 expression and decreased leptin and ObRb expression compared to AL mice. Mammary fat pads from tumor-free ICR-mice had higher adiponectin expression than AL and CCR mice while all tumor-bearing mice had weak adiponectin signal in mammary fat pad. Although we did not demonstrate an association of either adiponectin or leptin with individual mice in relation to mammary tumorigenesis, we did find that reduced serum leptin and elevated adiponectin:leptin ratio were associated with the protective effect of intermittent calorie restriction.