Pietiläinen Kirsi H, Kannisto Katja, Korsheninnikova Elena, Rissanen Aila, Kaprio Jaakko, Ehrenborg Ewa, Hamsten Anders, Yki-Järvinen Hannele
M.Sc., Obesity Research Unit, Biomedicum Helsinki, C428a, P.O. Box 700, FIN-00029 HUS, Finland.
J Clin Endocrinol Metab. 2006 Jul;91(7):2776-81. doi: 10.1210/jc.2005-2848. Epub 2006 Apr 11.
Both acquired and genetic factors regulate adipose tissue function.
We determined whether adipose tissue mRNA expression is regulated by obesity, independently of genetic effects, by studying monozygotic (MZ) twins.
Seventeen healthy pairs of MZ twins aged 24-27 yr (body mass index 20.0-33.9 kg/m(2), intrapair differences in body weight 0.1-24.7 kg), were identified from the population-based FinnTwin16 cohort. Body fat percent was determined by dual-energy x-ray absorptiometry, sc and intraabdominal fat by magnetic resonance imaging, liver fat by proton spectroscopy, and insulin sensitivity by using the euglycemic insulin clamp technique. Adipocyte cell size and expression of 10 genes (real-time PCR) were determined in sc adipose tissue biopsies. Serum levels of some of the genes were measured using ELISA.
Within MZ twin pairs, acquired obesity was significantly related to increased adipocyte size and increased adipose tissue mRNA expressions of leptin, TNFalpha and the macrophage marker CD68, and decreased mRNA expressions of adiponectin and peroxisome proliferator-activated receptor-gamma. Intrapair differences in liver fat correlated directly with those in leptin and CD68 expression. CD68 expression and serum TNFalpha concentrations were correlated with insulin resistance.
Acquired obesity independent of genetic influences is able to increase expression of macrophage and inflammatory markers and decrease adiponectin expression in adipose tissue.
获得性因素和遗传因素均调控脂肪组织功能。
通过研究同卵双胞胎,我们确定脂肪组织mRNA表达是否受肥胖调控,而不受遗传效应影响。
从基于人群的芬兰双胞胎16队列中识别出17对年龄在24 - 27岁的健康同卵双胞胎(体重指数20.0 - 33.9 kg/m²,双胞胎体重差异0.1 - 24.7 kg)。通过双能X线吸收法测定体脂百分比,通过磁共振成像测定皮下和腹部脂肪,通过质子光谱测定肝脏脂肪,并使用正常血糖胰岛素钳夹技术测定胰岛素敏感性。在皮下脂肪组织活检中测定脂肪细胞大小和10个基因的表达(实时PCR)。使用酶联免疫吸附测定法测量部分基因的血清水平。
在同卵双胞胎对中,获得性肥胖与脂肪细胞大小增加、脂肪组织中瘦素、肿瘤坏死因子α和巨噬细胞标志物CD68的mRNA表达增加以及脂联素和过氧化物酶体增殖物激活受体γ的mRNA表达降低显著相关。肝脏脂肪的双胞胎对间差异与瘦素和CD68表达的差异直接相关。CD68表达和血清肿瘤坏死因子α浓度与胰岛素抵抗相关。
独立于遗传影响的获得性肥胖能够增加脂肪组织中巨噬细胞和炎症标志物的表达,并降低脂联素表达。