Kolehmainen M, Salopuro T, Schwab U S, Kekäläinen J, Kallio P, Laaksonen D E, Pulkkinen L, Lindi V I, Sivenius K, Mager U, Siitonen N, Niskanen L, Gylling H, Rauramaa R, Uusitupa M
School of Public Health and Clinical Nutrition, Clinical Nutrition and Food and Health Research Center, University of Kuopio, Kuopio, Finland.
Int J Obes (Lond). 2008 Feb;32(2):292-303. doi: 10.1038/sj.ijo.0803718. Epub 2007 Sep 11.
Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome.
Randomized controlled and individualized weight reduction intervention.
Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 60+/-7 years were randomized either to a weight reduction (WR) (n=28) or a control (n=18) group lasting for 33 weeks.
Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction > or =5%, n=9) and control group (n=10). The results were confirmed using quantitative PCR.
In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S (I) and the change in body weight was found (r=-0.44, P=0.026). Downregulation of gene expression (P<0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (-39+/-16%, P<0.0001). Moreover, its expression correlated with insulin sensitivity (r=-0.34, P=0.005) before the intervention and with body adiposity both before (r=0.42, P=0.007) and after (r=0.30, P=0.056) the intervention.
Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.
生活方式和遗传因素在肥胖及代谢综合征的发生发展过程中相互作用。然而，有益饮食调整背后的分子机制尚不清楚。我们旨在研究长期适度减重对脂肪组织（AT）基因表达的影响，并确定对治疗有反应且可能导致代谢综合征发生的基因和基因簇。
随机对照和个体化减重干预。
46名空腹血糖受损或糖耐量受损且有代谢综合征特征的受试者，年龄60±7岁，被随机分为减重（WR）组（n = 28）或对照组（n = 18），干预持续33周。
在干预前后进行口服和静脉葡萄糖耐量试验以及皮下AT活检。在WR组（体重减轻≥5%，n = 9）和对照组（n = 10）的亚组中，使用微阵列技术研究AT的基因表达。结果通过定量PCR得到证实。
在WR组中，葡萄糖代谢得到改善。此外，发现S（I）的变化与体重变化之间存在负相关（r = -0.44，P = 0.026）。观察到涉及细胞外基质和细胞死亡基因本体组的基因表达下调（P < 0.01）。对照组未出现此类变化。腱调蛋白基因是下调最明显的基因之一（-39±16%，P < 0.0001）。此外，其表达在干预前与胰岛素敏感性相关（r = -0.34，P = 0.005），在干预前后均与身体肥胖相关（干预前r = 0.42，P = 0.007；干预后r = 0.30，P = 0.056）。
长期减重后，调节细胞外基质和细胞死亡的基因出现强烈下调。这可能反映了AT在分子水平上的一种新的稳定状态。有必要进一步研究以阐明这些遗传因素的机制。
