Department of Kinesiology, University of Maryland, School of Public Health, College Park, MD 21045, USA.
Am J Physiol Endocrinol Metab. 2013 Jun 1;304(11):E1199-212. doi: 10.1152/ajpendo.00617.2012. Epub 2013 Apr 2.
Reductions in estrogen function lead to adiposity and peripheral insulin resistance. Significant metabolic changes have been found in adipocytes and skeletal muscle with disruptions in the estrogen-signaling axis; however, it is unclear if intercellular communication exists between these tissues. The purpose of this study was to examine the impact of isolated adipocytes cocultured with single adult skeletal muscle fibers (SMF) collected from control female (SHAM) and ovariectomized female (OVX) mice. In addition, a second purpose was to compare differential effects of primary adipocytes from omental and inguinal adipose depots on SMF from these same groups. OVX SMF displayed greater lipid content, impaired insulin signaling, and lower insulin-induced glucose uptake compared with SHAM SMF without coculture. In the SHAM group, regardless of the adipose depot of origin, coculture induced greater intracellular lipid content compared with control SHAM SMF. The increased lipid in the SMF was associated with impaired insulin-induced glucose uptake when adipocytes were of omental, but not inguinal, origin. Coculture of OVX SMF with omental or inguinal adipocytes resulted in higher lipid content but no further reduction in insulin-induced glucose uptake compared with control OVX SMF. The data indicate that, in the OVX condition, there is a threshold for lipid accumulation in skeletal muscle beyond which there is no further impairment in insulin responsiveness. These results also demonstrate depot-specific effects of adipocyte exposure on skeletal muscle glucose uptake and further implicate a role for increased intracellular lipid storage in the pathogenesis of insulin resistance when estrogen levels are reduced.
雌激素功能的降低会导致脂肪堆积和外周胰岛素抵抗。在脂肪细胞和骨骼肌中发现了与雌激素信号轴中断相关的显著代谢变化；然而，尚不清楚这些组织之间是否存在细胞间通讯。本研究的目的是研究分离的脂肪细胞与从对照雌性（SHAM）和去卵巢雌性（OVX）小鼠中收集的单个成年骨骼肌纤维（SMF）共培养对的影响。此外，第二个目的是比较来自网膜和腹股沟脂肪垫的原代脂肪细胞对来自这些相同组的 SMF 的不同影响。与未共培养的 SHAM SMF 相比，OVX SMF 显示出更高的脂质含量、受损的胰岛素信号和更低的胰岛素诱导的葡萄糖摄取。在 SHAM 组中，无论脂肪垫的来源如何，共培养都导致与对照 SHAM SMF 相比，细胞内脂质含量增加。当脂肪细胞来源于网膜而不是腹股沟时，SMF 中的增加的脂质与胰岛素诱导的葡萄糖摄取受损有关。与对照 OVX SMF 相比，OVX SMF 与网膜或腹股沟脂肪细胞共培养导致更高的脂质含量，但胰岛素诱导的葡萄糖摄取没有进一步降低。数据表明，在 OVX 状态下，骨骼肌中的脂质积累存在一个阈值，超过这个阈值，胰岛素反应性就不会进一步受损。这些结果还表明，脂肪细胞暴露对骨骼肌葡萄糖摄取具有特定脂肪垫的影响，并进一步表明当雌激素水平降低时，细胞内脂质储存增加在胰岛素抵抗的发病机制中起作用。
