Forced catch-up growth after fetal protein restriction alters the adipose tissue gene expression program leading to obesity in adult mice
Forced catch-up growth after fetal protein restriction alters the adipose tissue gene expression program leading to obesity in adult mice
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DOI：
10.1152/ajpregu.90497.2008
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发表时间：
2009-08-01
影响因子：
2.8
通讯作者：
Remacle, C.
中科院分区：
文献类型：
--
作者：
Bol, V. V.;Delattre, A-I.;Remacle, C.
Bol VV，Delattre AI，Reusens B，Raes M，Remacle C.胎儿蛋白限制后的强制追赶生长改变了脂肪组织基因表达程序，导致成年小鼠肥胖。Am J Physiol Regul Integr Comp Physiol 297：R291-R299，2009。首次发表于2009年5月20日; doi：10.1152/ajpregu.90497.2008。流行病学研究表明，胎儿和出生后环境之间的不匹配可能永久性地改变身体结构和生理机能，从而导致后来的肥胖和相关疾病。脂肪组织的早期编程可能是这一观察的核心。此外，脂肪组织分泌脂肪因子，提供肥胖和其相关疾病之间的分子联系。因此，我们的目的是研究在胎儿期蛋白质限制，随后追赶生长是否会导致9个月大的雄性小鼠肥胖，并改变脂肪组织基因表达谱。妊娠期间，母鼠喂食低蛋白（LP）或等热量对照（C）饲料。通过用对照饮食喂养母鼠和将LP窝仔剔除至4只幼仔而不是C组的8只幼仔，诱导LP后代的产后追赶生长。在断奶时，雄性小鼠仅通过实验室食物（C）或补充有高热量饮食（HC）来喂养，以诱导肥胖（C-C、C-HC、LP-C和LP-HC组）。在9个月时，LP后代的特征是相对脂肪量增加、高血糖、高胆固醇血症和高瘦素血症。使用设计的微阵列来研究参与脂肪组织分化/功能的89个基因的表达，我们证明了几个基因的表达谱依赖于母体饮食。在不同的基因表现出改变的表达，我们可以确定基因编码的几种酶参与脂质代谢。这些结果表明，后代提交的早期不匹配的营养表现出脂肪组织基因表达的改变，可能会增加他们的易感性超重时，挑战断奶后的HC饮食。
Bol VV, Delattre AI, Reusens B, Raes M, Remacle C. Forced catch-up growth after fetal protein restriction alters the adipose tissue gene expression program leading to obesity in adult mice. Am J Physiol Regul Integr Comp Physiol 297: R291-R299, 2009. First published May 20, 2009; doi:10.1152/ajpregu.90497.2008.-A mismatch between fetal and postnatal environment can permanently alter the body structure and physiology and therefore contribute later to obesity and related disorders, as revealed by epidemiological studies. Early programming of adipose tissue might be central in this observation. Moreover, adipose tissue secretes adipokines that provide a molecular link between obesity and its related disorders. Therefore, our aim was to investigate whether a protein restriction during fetal life, followed by catch-up growth could lead to obesity in 9-mo-old male mice and could alter the adipose tissue gene expression profile. Dams were fed a low-protein (LP) or an isocaloric control (C) diet during gestation. Postnatal catch-up growth was induced in LP offspring by feeding dams with control diet and by culling LP litters to four pups instead of eight in the C group. At weaning, male mice were fed by lab chow alone (C) or supplemented with a hypercaloric diet (HC), to induce obesity (C-C, C-HC, LP-C, and LP-HC groups). At 9 mo, LP offspring featured increased relative fat mass, hyperglycemia, hypercholesterolemia, and hyperleptinemia. Using a microarray designed to study the expression of 89 genes involved in adipose tissue differentiation/function, we demonstrated that the expression profile of several genes were dependent upon the maternal diet. Among the diverse genes showing altered expression, we could identify genes encoding several enzymes involved in lipid metabolism. These results indicated that offspring submitted to early mismatched nutrition exhibited alterations in adipose tissue gene expression that probably increases their susceptibility to overweight when challenged after weaning with a HC diet.