ABSTRACT

Adipose tissue plays a major role in regulating whole-body energy metabolism. While the biochemical processes regulating storage and release of excess energy are well known, the temporal organization of these events is much less defined. In this study, we have characterized the presence of small surface-associated lipid droplets, distinct from the central droplet, in primary human adipocytes. Based on microscopy analyses, we illustrate the distribution of mitochondria, endoplasmic reticulum and lysosomes in the vicinity of these specialized lipid droplets. Ultrastructure analysis confirmed the presence of small droplets in intact adipose tissue. Further, CIDEC, known to bind and regulate lipid droplet expansion, clearly localized at these lipid droplets. Neither acute or prolonged stimulation with insulin or isoprenaline, or pharmacologic intervention to suppress lipid flux, affected the presence of these lipid droplets. Still, phosphorylated perilipin and hormone-sensitive lipase accumulated at these droplets following adrenergic stimuli, which supports metabolic activity at these locations. Altogether, we propose these lipid droplet clusters represent an intermediate site involved in lipid transport in primary adipocytes.

摘要

脂肪组织在调节全身能量代谢中起主要作用。尽管调节过量能量的储存和释放的生化过程是众所周知的，但是这些事件的时间组织却很少定义。在这项研究中，我们表征了原发性人类脂肪细胞中与中央液滴不同的表面相关脂质小液滴的存在。基于显微镜分析，我们说明了这些专门脂质滴附近的线粒体，内质网和溶酶体的分布。超微结构分析证实完整的脂肪组织中存在小液滴。此外，已知结合并调节脂质小滴膨胀的CIDEC明显位于这些脂质小滴处。不论是胰岛素或异丙肾上腺素的急性或长期刺激，或通过药物干预抑制脂质通量，影响了这些脂质液滴的存在。尽管如此，在肾上腺素能刺激后，磷酸化的脂蛋白和激素敏感性脂肪酶会在这些小滴处积聚，从而支持这些位置的代谢活性。总之，我们提出这些脂质小滴簇代表初级脂肪细胞中参与脂质转运的中间位点。