Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Denmark.
J Appl Physiol (1985). 2011 Dec;111(6):1863-70. doi: 10.1152/japplphysiol.00960.2011. Epub 2011 Sep 8.
Intrauterine growth retardation (IUGR) is associated with a central fat distribution and risk of developing type 2 diabetes in adults when exposed to a sedentary Western lifestyle. Increased lipolysis is an early defect of metabolism in IUGR subjects, but the sites and molecular mechanisms involved are unknown. Twenty IUGR and 20 control (CON) subjects, aged 20-30 years, were studied before and after 10 days of bed rest using the glucose clamp technique combined with measurements of in vivo metabolism by microdialysis technique and blood flow by (133)Xe washout technique in subcutaneous abdominal (SCAAT) and femoral (SCFAT) adipose tissue. Additionally, mRNA expression of lipases was evaluated in biopsies from SCAAT. Lipolysis in SCAAT was substantially higher in IUGR than in CON subjects despite markedly lower mRNA expression of lipases. Blood flow was higher in IUGR compared with CON in both SCAAT and SCFAT. Whole body insulin sensitivity did not differ between groups and decreased after bed rest. After bed rest, SCAAT lipolysis remained higher in IUGR compared with CON, and SCFAT lipolysis decreased in CON but not in IUGR. Prior to the development of whole body insulin resistance, young men with IUGR are characterized by increased in vivo adipose tissue lipolysis and blood flow with a paradoxically decreased expression of lipases compared with CON, and 10 days of physical inactivity underlined the baseline findings. Subjects with IUGR exhibit primary defects in adipose tissue metabolism.
宫内发育迟缓(IUGR)与中心性脂肪分布有关,并且在接触到西方久坐不动的生活方式时,成年人患 2 型糖尿病的风险增加。在 IUGR 患者中,脂肪分解增加是代谢的早期缺陷,但涉及的部位和分子机制尚不清楚。研究了 20 名 IUGR 和 20 名对照(CON)受试者,年龄在 20-30 岁之间,在卧床休息 10 天前后使用葡萄糖钳夹技术结合微透析技术测量体内代谢和(133)Xe 洗脱技术测量皮下腹部(SCAAT)和股部(SCFAT)脂肪组织的血流量。此外,还评估了 SCAAT 活检中脂肪酶的 mRNA 表达。尽管 SCAAT 中的脂肪酶 mRNA 表达明显较低,但 IUGR 中的脂肪分解率明显高于 CON 组。与 CON 相比,IUGR 的 SCAAT 和 SCFAT 中的血流量均较高。两组之间的全身胰岛素敏感性没有差异,并且在卧床休息后下降。卧床休息后,IUGR 中 SCAAT 的脂肪分解率仍高于 CON,而 CON 中的 SCFAT 脂肪分解率下降,但 IUGR 中没有下降。在全身胰岛素抵抗发展之前,IUGR 的年轻男性表现为体内脂肪组织脂肪分解和血流量增加,而脂肪酶的表达却异常降低,与 CON 相比,10 天的体力活动不足强调了基线发现。IUGR 患者表现出脂肪组织代谢的主要缺陷。