Wadley Glenn D, Siebel Andrew L, Cooney Greg J, McConell Glenn K, Wlodek Mary E, Owens Julie A
Department of Physiology, The University of Melbourne, Parkville, Australia.
Am J Physiol Endocrinol Metab. 2008 May;294(5):E861-9. doi: 10.1152/ajpendo.00037.2008. Epub 2008 Mar 4.
Uteroplacental insufficiency has been shown to impair insulin action and glucose homeostasis in adult offspring and may act in part via altered mitochondrial biogenesis and lipid balance in skeletal muscle. Bilateral uterine vessel ligation to induce uteroplacental insufficiency in offspring (Restricted) or sham surgery was performed on day 18 of gestation in rats. To match the litter size of Restricted offspring, a separate cohort of sham litters had litter size reduced to five at birth (Reduced Litter), which also restricted postnatal growth. Remaining litters from sham mothers were unaltered (Control). Offspring were studied at 6 mo of age. In males, both Restricted and Reduced Litter offspring had reduced gastrocnemius PPARgamma coactivator-1alpha (PGC-1alpha) mRNA and protein, and mitochondrial transcription factor A (mtTFA) and cytochrome oxidase (COX) III mRNA (P < 0.05), whereas only Restricted had reduced skeletal muscle COX IV mRNA and protein and glycogen (P < 0.05), despite unaltered glucose tolerance, homeostasis model assessment (HOMA) and intramuscular triglycerides. In females, only gastrocnemius mtTFA mRNA was lower in Reduced Litter offspring (P < 0.05). Furthermore, glucose tolerance was not altered in any female offspring, although HOMA and intramuscular triglycerides increased in Restricted offspring (P < 0.05). It is concluded that restriction of growth due to uteroplacental insufficiency alters skeletal muscle mitochondrial biogenesis and metabolic characteristics, such as glycogen and lipid levels, in a sex-specific manner in the adult rat in the absence of impaired glucose tolerance. Furthermore, an adverse postnatal environment induced by reducing litter size also restricts growth and alters skeletal muscle mitochondrial biogenesis and metabolic characteristics in the adult rat.
子宫胎盘功能不全已被证明会损害成年后代的胰岛素作用和葡萄糖稳态，并且可能部分通过改变骨骼肌中的线粒体生物合成和脂质平衡来发挥作用。在大鼠妊娠第18天进行双侧子宫血管结扎，以诱导后代出现子宫胎盘功能不全（受限组）或假手术。为了使受限组后代的窝仔数相匹配，将另一组假手术产仔的窝仔数在出生时减少到5只（减少窝仔数组），这也限制了出生后的生长。假手术母亲剩余的窝仔未作处理（对照组）。在6月龄时对后代进行研究。在雄性后代中，受限组和减少窝仔数组的腓肠肌过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）mRNA和蛋白、线粒体转录因子A（mtTFA）和细胞色素氧化酶（COX）III mRNA均减少（P<0.05），而只有受限组的骨骼肌COX IV mRNA和蛋白以及糖原减少（P<0.05），尽管葡萄糖耐量、稳态模型评估（HOMA）和肌肉内甘油三酯未改变。在雌性后代中，只有减少窝仔数组的腓肠肌mtTFA mRNA较低（P<0.05）。此外，尽管受限组后代的HOMA和肌肉内甘油三酯增加（P<0.05），但任何雌性后代的葡萄糖耐量均未改变。研究得出结论，在成年大鼠中，子宫胎盘功能不全导致的生长受限会以性别特异性方式改变骨骼肌线粒体生物合成和代谢特征，如糖原和脂质水平，且不存在葡萄糖耐量受损的情况。此外，减少窝仔数所诱导的不良出生后环境也会限制成年大鼠的生长，并改变骨骼肌线粒体生物合成和代谢特征。
