Boullu-Ciocca Sandrine, Achard Vincent, Tassistro Virginie, Dutour Anne, Grino Michel
INSERM U626, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France.
Diabetes. 2008 Mar;57(3):669-77. doi: 10.2337/db07-1316. Epub 2007 Dec 5.
Alterations of the perinatal environment, which lead to increased prevalence of the metabolic syndrome in adulthood, program an upregulation of systemic and/or adipose tissue glucocorticoid metabolism (11 beta-hydroxysteroid dehydrogenase type 1 [11 beta-HSD-1]-induced corticosterone reactivation). We hypothesized that postnatal programming could modulate high-fat diet-induced adipose tissue dysregulation in adulthood.
We compared the effects of chronic (since weaning) high- or low-fat diet in postnatally normofed (control) or overfed (programmed) rats.
Postnatal programming accentuated high-fat diet-induced overweight, insulin resistance, glucose intolerance, and decrease in circulating and epididymal adipose tissue adiponectin. Neither manipulation altered liver function. Postnatal programming or high-fat diet increased systemic corticosterone production, which was not further modified when both manipulations were associated. Postnatal programming suppressed high-fat diet-induced decrease in mesenteric adipose tissue (MAT) glucocorticoid sensitivity and triggered high-fat diet-induced increase in MAT glucocorticoid exposure, subsequent to enhanced MAT 11 beta-HSD-1 gene expression. MAT tumor necrosis factor (TNF)-alpha, TNF-receptor 1, interleukin (IL)-6, resistin, and plasminogen activator inhibitor-1 mRNAs were not changed by high-fat feeding in control rats and showed a large increase in programmed animals, with this effect further enhanced by high-fat diet for TNF-alpha and IL-6.
Our data show for the first time that postnatal manipulation programs high-fat diet-induced upregulation of MAT glucocorticoid exposure, sensitivity, and inflammatory status and therefore reveal the pivotal role of the environment during the perinatal period on the development of diet-induced adipose tissue dysregulation in adulthood. They also urge the need for clinical trials with specific 11 beta-HSD-1 inhibitors.
围产期环境的改变会导致成年期代谢综合征患病率增加,这种改变会使全身和/或脂肪组织糖皮质激素代谢上调(11β-羟基类固醇脱氢酶1型[11β-HSD-1]诱导的皮质酮再激活)。我们推测出生后编程可能会调节成年期高脂饮食诱导的脂肪组织失调。
我们比较了出生后正常喂养(对照)或过度喂养(编程)大鼠长期(自断奶起)高脂或低脂饮食的影响。
出生后编程加剧了高脂饮食诱导的超重、胰岛素抵抗、葡萄糖不耐受以及循环和附睾脂肪组织脂联素的降低。两种处理均未改变肝功能。出生后编程或高脂饮食会增加全身皮质酮的产生,当两种处理同时进行时,这种增加并未进一步改变。出生后编程抑制了高脂饮食诱导的肠系膜脂肪组织(MAT)糖皮质激素敏感性降低,并在MAT 11β-HSD-1基因表达增强后引发了高脂饮食诱导的MAT糖皮质激素暴露增加。对照大鼠高脂喂养时,MAT肿瘤坏死因子(TNF)-α、TNF受体1、白细胞介素(IL)-6、抵抗素和纤溶酶原激活物抑制剂-1的mRNA未发生变化,而在编程动物中大幅增加,高脂饮食对TNF-α和IL-6的这种作用进一步增强。
我们的数据首次表明,出生后处理会使高脂饮食诱导的MAT糖皮质激素暴露、敏感性和炎症状态上调,因此揭示了围产期环境在成年期饮食诱导的脂肪组织失调发展中的关键作用。它们还促使有必要进行使用特定11β-HSD-1抑制剂的临床试验。