Van Schothorst Evert M, Franssen-van Hal Nicole, Schaap Mirjam M, Pennings Jeroen, Hoebee Barbara, Keijer Jaap
Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands.
Obes Res. 2005 Jun;13(6):1031-41. doi: 10.1038/oby.2005.121.
To identify early molecular changes in weight gain, using analysis of gene expression changes in adipose tissue of mice fed well-defined humanized (Western) high-fat and low-fat (control) diets during a short (3- to 5-week) time interval.
An adipose-enriched cDNA microarray was constructed and used for the expression analyses of visceral adipose tissues of wildtype young adult C57BL/6J male mice on different diets.
Mice on a high-fat diet had significantly higher body weight (at most, 9.6% greater) and adipose tissue weights compared with mice on a control diet. Gene expression analyses revealed 31 transcripts significantly differentially expressed in visceral adipose tissue between the diet groups. Most of these genes were expressed more on the high-fat diet. They mainly encode proteins involved in cellular structure (e.g., myosin, procollagen, vimentin) and lipid metabolism (e.g., leptin, lipoprotein lipase, carbonic anhydrase 3). This increase in gene expression was accompanied by a decrease in oxidative phosphorylation and carbohydrate metabolism (ATP citrate lyase). Importantly, genes belonging to steroid hormone biosynthesis (3beta-hydroxysteroid dehydrogenase-1, cholesterol side-chain cleavage cytochrome P450, and steroid-11beta-hydroxylase) were all expressed less in mice on a high-fat diet.
A short time period of 3 to 5 weeks of high-fat feeding altered gene expression patterns in visceral adipose tissue in male mice. Gene expression changes indicate initiation of adipose tissue enlargement and the down-regulation of adipose steroid hormone biosynthesis. The latter suggests a mechanism by which initial progression toward weight gain is counteracted.
通过分析在短时间（3至5周）内喂食明确的人源化（西式）高脂和低脂（对照）饮食的小鼠脂肪组织中的基因表达变化，来确定体重增加早期的分子变化。
构建了一个富含脂肪的cDNA微阵列，并用于分析不同饮食条件下野生型成年C57BL/6J雄性小鼠内脏脂肪组织的表达情况。
与对照饮食组的小鼠相比，高脂饮食组的小鼠体重显著更高（最多高9.6%），脂肪组织重量也更大。基因表达分析显示，饮食组之间内脏脂肪组织中有31种转录本存在显著差异表达。这些基因中的大多数在高脂饮食中表达更多。它们主要编码参与细胞结构（如肌球蛋白、前胶原、波形蛋白）和脂质代谢（如瘦素、脂蛋白脂肪酶、碳酸酐酶3）的蛋白质。基因表达的这种增加伴随着氧化磷酸化和碳水化合物代谢（ATP柠檬酸裂解酶）的减少。重要的是，属于类固醇激素生物合成的基因（3β-羟基类固醇脱氢酶-1、胆固醇侧链裂解细胞色素P450和类固醇11β-羟化酶）在高脂饮食的小鼠中表达均较少。
3至5周的高脂喂养短时间内改变了雄性小鼠内脏脂肪组织中的基因表达模式。基因表达变化表明脂肪组织开始增大，且脂肪类固醇激素生物合成下调。后者提示了一种抵消体重增加初始进程的机制。
