Diet and gene interactions influence the skeletal response to polyunsaturated fatty acids.
Diet and gene interactions influence the skeletal response to polyunsaturated fatty acids.
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DOI：
10.1016/j.bone.2014.07.024
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发表时间：
2014-11
期刊：
影响因子：
4.1
通讯作者：
Rosen, Clifford J.
中科院分区：
文献类型：
--
作者：
Bonnet, Nicolas;Somm, Emmanuel;Rosen, Clifford J.
富含omega-3脂肪酸的饮食被认为可以预防肥胖和骨质疏松症。然而，相互矛盾的研究结果报告，可能是由于基因营养相互作用。过氧化物酶体增殖物激活受体-γ（过氧化物酶体增殖物激活受体γ）是一种核受体，其改善胰岛素敏感性但引起体重增加和骨丢失。鱼油是一种天然的过氧化物酶体增殖物激活体受体γ激动剂，因此可能通过过氧化物酶体增殖物激活体受体γ途径发挥其作用。我们使用两个品系的C57 BL 6 J（B6），即B6. C3 H-6 T（6 T）同源小鼠和C57 BL 6 J小鼠，通过将携带Pparγ基因中“功能获得”多态性的C3 H的Chr 6上的一个小位点回交到B6背景中而产生，来检测PPARγ在鱼油或红花油饮食诱导的身体组成变化中的作用。在给雌性小鼠喂食两种饮食9个月后，喂食鱼油的小鼠的体重、脂肪百分比和瘦素水平低于喂食红花油的小鼠，与基因型无关。在骨骼水平上，鱼油保存了B6小鼠的脊椎骨矿物质密度（BMD）和微观结构，但在6 T小鼠中没有。此外，鱼油消耗与骨髓肥胖的增加和BMD，皮质厚度，极限力和股骨的塑性能的6 T，但不是B6小鼠的减少。这些作用导致6 T中脂肪形成炎症和吸收标志物增加，但B6中没有。因此，与红花油相比，鱼油（高比例ω-3/-6）可防止体重增加，骨质流失和脊柱中骨小梁微结构随年龄的变化。这些有益作用在Pparγ基因（6 T）多态性小鼠中不存在，支持n-3脂肪酸对骨微结构的作用可能具有基因型依赖性的原则。因此，在解释小鼠和人类骨骼终点的饮食干预试验时必须谨慎。
Diets rich in omega-3s have been thought to prevent both obesity and osteoporosis. However, conflicting findings are reported, probably as a result of gene by nutritional interactions. Peroxisome proliferator-activated receptor-gamma (PPARγ), is a nuclear receptor that improves insulin sensitivity but causes weight gain and bone loss. Fish oil is a natural agonist for PPARγ and thus may exert its actions through PPARγ pathway. We examined the role of PPARγ in body composition changes induced by a fish or safflower oil diet using two strains of C57BL6J (B6); i.e. B6.C3H-6T (6T) congenic mice created by backcrossing a small locus on Chr 6 from C3H carrying ‘gain of function’ polymorphisms in the Pparγ gene onto a B6 background, and C57BL6J mice. After 9 months of feeding both diets to female mice, body weight, percent fat and leptin levels were less in mice fed the fish oil vs those fed safflower oil, independent of genotype. At the skeletal level, fish oil preserved vertebral bone mineral density (BMD) and microstructure in B6 but not in 6T mice. Moreover, fish oil consumption was associated with an increase in bone marrow adiposity and a decrease in BMD, cortical thickness, ultimate force and plastic energy in femur of the 6T but not B6 mice. These effects paralleled an increase in adipogenic inflammatory and resorption markers in 6T but not B6. Thus, compared to safflower oil, fish oil (high ratio omega-3/-6) prevents weight gain, bone loss, and changes in trabecular microarchitecture in the spine with age. These beneficial effects are absent in mice with polymorphisms in the Pparγ gene (6T), supporting the tenet that the actions of n-3 fatty acids on bone microstructure are likely to be genotype dependent. Thus caution must be used in interpreting dietary intervention trials with skeletal endpoints in mice and in humans.
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影响因子：
4.7
作者：
Golub, N.;Geba, D.;Mousa, S. A.;Williams, G.;Block, R. C.
通讯作者：
Block, R. C.
影响因子：
4.2
作者：
Farina, Emily K.;Kiel, Douglas P.;Tucker, Katherine L.
通讯作者：
Tucker, Katherine L.
影响因子：
4.1
作者：
Hamrick, MW;Pennington, C;Isales, C
通讯作者：
Isales, C
影响因子：
4.8
作者：
Le, Phuong;Kawai, Masanobu;Rosen, Clifford J.
通讯作者：
Rosen, Clifford J.
影响因子：
6.2
作者：
Ackert-Bicknell, Cheryl L.;Demissie, Serkalem;Rosen, Clifford J.
通讯作者：
Rosen, Clifford J.