Muhlhausler B S, Ritorto V, Schultz C, Chatterton B E, Duffield J A, McMillen I C
Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide 5000, Australia.
Domest Anim Endocrinol. 2008 Jul;35(1):46-57. doi: 10.1016/j.domaniend.2008.01.007. Epub 2008 Feb 20.
Epidemiological studies have demonstrated that low birth weight is associated with an increased incidence of visceral obesity and metabolic disorders in later life. In the present study, we have determined the impact of birth weight and gender on gene expression in visceral adipose tissue (VAT) in the young adult sheep. Lambs (n=19, birth weight range 2.6-7.55 kg) were born at term and growth monitored for 22.4+/-0.2 weeks, when body composition was determined by Dual X-ray Absorptiometry (DXA) and samples of VAT and subcutaneous (SCAT) adipose tissue collected. Plasma samples were collected at post-mortem for the determination of free fatty acids (FFA), glucose and insulin concentrations. Peroxisome-Proliferator Activated Receptor-gamma (PPARgamma), glycerol-3-phosphate dehydrogenase (G3PDH), lipoprotein lipase (LPL), adiponectin and leptin mRNA expression was determined by qRT-PCR. Fractional growth rate in postnatal weeks 1-3 was inversely related to birth weight in both males and females (R2=0.22, P<0.05, n=19). PPARgamma mRNA expression in VAT, but not SCAT, was inversely related to birth weight (R2=0.60, P<0.01, n=18). In males, but not females, PPARgamma mRNA in VAT was directly related to G3PDH mRNA expression (R2=0.69, P<0.01, n=9). Plasma FFA concentrations were inversely related to birth weight in both males and females (R2=0.22, P<0.05, n=19). These findings demonstrate that low birth weight is associated with an increased expression of a key adipogenic factor in visceral adipose tissue in young adulthood. In males, this is associated with an increased expression of lipogenic genes, and this may contribute to the increased propensity for visceral obesity in low birth weight males compared to females.
流行病学研究表明，低出生体重与成年后期内脏肥胖和代谢紊乱的发病率增加有关。在本研究中，我们确定了出生体重和性别对年轻成年绵羊内脏脂肪组织（VAT）中基因表达的影响。羔羊（n = 19，出生体重范围2.6 - 7.55千克）足月出生，并监测生长22.4±0.2周，此时通过双能X线吸收法（DXA）测定身体成分，并采集VAT和皮下（SCAT）脂肪组织样本。死后采集血浆样本，用于测定游离脂肪酸（FFA）、葡萄糖和胰岛素浓度。通过qRT-PCR测定过氧化物酶体增殖物激活受体γ（PPARγ）、甘油-3-磷酸脱氢酶（G3PDH）、脂蛋白脂肪酶（LPL）、脂联素和瘦素mRNA的表达。出生后第1 - 3周的生长分数率在雄性和雌性中均与出生体重呈负相关（R2 = 0.22，P < 0.05，n = 19）。VAT中PPARγ mRNA的表达与出生体重呈负相关，但SCAT中并非如此（R2 = 0.60，P < 0.01，n = 18）。在雄性而非雌性中，VAT中的PPARγ mRNA与G3PDH mRNA的表达直接相关（R2 = 0.69，P < 0.01，n = 9）。血浆FFA浓度在雄性和雌性中均与出生体重呈负相关（R2 = 0.22，P < 0.05，n = 19）。这些发现表明，低出生体重与年轻成年期内脏脂肪组织中关键脂肪生成因子的表达增加有关。在雄性中，这与脂肪生成基因的表达增加有关，这可能导致低出生体重雄性与雌性相比内脏肥胖倾向增加。
