Maternal obesity induces gut inflammation and impairs gut epithelial barrier function in nonobese diabetic mice.
Maternal obesity induces gut inflammation and impairs gut epithelial barrier function in nonobese diabetic mice.
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DOI：
10.1016/j.jnutbio.2014.03.009
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发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
Zhu MJ
中科院分区：
文献类型：
--
作者：
Xue Y;Wang H;Du M;Zhu MJ
肠上皮屏障功能受损是炎症性肠病、1型糖尿病（T1 D）和相关自身免疫性疾病的关键诱发因素。我们假设母体肥胖诱导非肥胖糖尿病（NOD）小鼠后代的肠道炎症和上皮屏障功能受损。用对照饮食（CON，10%来自脂肪的能量）或高脂肪饮食（HFD，60%来自脂肪的能量）喂养4周龄雌性NOD/ShiLtJ小鼠8周以诱导肥胖，然后交配。在妊娠和哺乳期间，小鼠维持在各自的饮食中。断奶后，所有的后代都被喂食CON饮食。在16周龄时，对雌性后代进行体内肠渗透性试验，然后对回肠取样进行生化分析。肥胖母亲的后代中炎症介质、活化的caspase-1以及成熟形式的白细胞介素（IL）-1β和IL-18增强，这与血清肿瘤坏死因子（TNF）α水平升高和炎症介质相关。与对照组相比，仔鼠回肠组织中过氧化氢酶、过氧化物酶-4和超氧化物歧化酶-1的含量显著升高（P < 0.05）。此外，肥胖母亲的后代具有更高的肠道通透性。从形态学上看，母体肥胖降低了后代肠道回肠中的绒毛/隐窝比例。总之，母体肥胖诱导NOD小鼠后代的炎症和肠道屏障功能受损。HFD后代中增强的肠道渗透性可能使其易于发展T1 D和其他肠道渗透性相关疾病。
Impairment of gut epithelial barrier function is a key predisposing factor for inflammatory bowel disease, type 1 diabetes (T1D), and related autoimmune diseases. We hypothesized that maternal obesity induces gut inflammation and impairs epithelial barrier function in the offspring of non-obese diabetic (NOD) mice. 4-week-old female NOD/ShiLtJ mice were fed with a control diet (CON, 10% energy from fat) or a high fat diet (HFD, 60% energy from fat) for 8 weeks to induce obesity and then mated. During pregnancy and lactation, mice were maintained in their respective diets. After weaning, all offspring were fed the CON diet. At 16 weeks of age, female offspring were subjected to in vivo intestinal permeability test and, then, ileum was sampled for biochemical analyses. Inflammasome mediators, activated caspase-1 as well as mature forms of interleukin (IL) -1β and IL-18 were enhanced in offspring of obese mothers, which was associated with elevated serum tumor necrosis factor (TNF)α level and inflammatory mediators. Consistently, abundance of oxidative stress markers including catalase, peroxiredoxin-4 and superoxide dismutase 1 were heightened in offspring ileum (P < 0.05). Furthermore, offspring from obese mothers had a higher intestinal permeability. Morphologically, maternal obesity reduced villi/crypt ratio in the ileum of offspring gut. In conclusion, maternal obesity induced inflammation and impaired gut barrier function in offspring of NOD mice. The enhanced gut permeability in HFD offspring might pre-dispose them to the development of T1D and other gut permeability associated diseases.
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