Department of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
J Nutr. 2012 May;142(5):859-65. doi: 10.3945/jn.111.149914. Epub 2012 Mar 21.
Male and female C57Bl6 mice were fed a control AIN76A diet, a new Western-style diet (NWD1) reflecting dietary patterns linked to elevated colon cancer incidence (higher fat, lower cholecalciferol, calcium, methyl donors, fiber), or NWD1 with elevated cholecalciferol and calcium (NWD2) from weaning. After 24 wk, serum 25-hydroxyvitamin D [25(OH)D] decreased by >80% in the NWD1 group compared with controls, but with no alteration in serum calcium or bone mineral density. The decreased serum 25(OH)D was prevented in the NWD2 group. After 32 wk, the NWD1 group compared with controls reduced overall energy expenditure by 15% without altering food consumption or physical activity and induced glucose intolerance, phenotypes associated with metabolic syndrome. These responses were unexpectedly exacerbated in the NWD2 group, further shifting mice toward greater fatty acid storage rather than oxidation compared with both control and NWD1 groups, but there was no change in physical activity, causing significant weight gain due to increased fat mass. The NWD1 group also exhibited inflammatory responses compared with controls, including macrophage-associated crown-like structures in epididymal adipose tissue and increased serum concentrations of the proinflammatory cytokine IL-1β, and of its targets, MCP-1 and Rantes, which were prevented or greatly mitigated in the NWD2 group. However, there was also elevated lipid storage in the liver and steatosis not seen in the control and NWD1 groups. Thus, elevating cholecalciferol and calcium in a Western-style diet can reduce inflammation associated with risk for colon tumor development, but interaction of nutrients in this diet can compromise liver function when fed long term.
雄性和雌性 C57Bl6 小鼠在断奶后分别喂食对照 AIN76A 饮食、新的西式饮食（NWD1，反映与结肠癌发病率升高相关的饮食模式，即高脂肪、低胆钙化醇、钙、甲基供体、纤维）或高胆钙化醇和钙的 NWD1（NWD2）。24 周后，与对照组相比，NWD1 组血清 25-羟维生素 D[25(OH)D]降低超过 80%，但血清钙或骨密度没有改变。NWD2 组可预防血清 25(OH)D 降低。32 周后，与对照组相比，NWD1 组总能量消耗降低 15%，而食物摄入或体力活动没有改变，并导致葡萄糖不耐受，这是代谢综合征的相关表型。与对照组相比，这些反应在 NWD2 组出乎意料地加剧，与对照组和 NWD1 组相比，进一步使小鼠更倾向于储存脂肪酸而不是氧化脂肪酸，但体力活动没有改变，导致由于脂肪量增加而显著体重增加。与对照组相比，NWD1 组还表现出炎症反应，包括附睾脂肪组织中与巨噬细胞相关的冠状样结构和促炎细胞因子 IL-1β及其靶标 MCP-1 和 Rantes 的血清浓度升高，而 NWD2 组可预防或大大减轻这些反应。然而，肝脏中的脂质储存也增加，出现了对照组和 NWD1 组未观察到的脂肪变性。因此，在西式饮食中提高胆钙化醇和钙可以降低与结肠癌发展风险相关的炎症，但当长期喂食时，这种饮食中营养素的相互作用可能会损害肝功能。
