Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-8549, USA.
Am J Pathol. 2010 Mar;176(3):1364-76. doi: 10.2353/ajpath.2010.090647. Epub 2010 Jan 21.
Metabolically healthy individuals effectively adapt to changes in nutritional state. Here, we focus on the effects of the adipocyte-derived secretory molecule adiponectin on adipose tissue in mouse models with genetically altered adiponectin levels. We found that higher adiponectin levels increased sensitivity to the lipolytic effects of adrenergic receptor agonists. In parallel, adiponectin-overexpressing mice also display enhanced clearance of circulating fatty acids and increased expansion of subcutaneous adipose tissue with chronic high fat diet (HFD) feeding. These adaptive changes to the HFD were associated with increased mitochondrial density in adipocytes, smaller adipocyte size, and a general transcriptional up-regulation of factors involved in lipid storage through efficient esterification of free fatty acids. The physiological response to adiponectin overexpression resembles in many ways the effects of chronic exposure to beta3-adrenergic agonist treatment, which also results in improvements in insulin sensitivity. In addition, using a novel computed tomography-based method for measurements of hepatic lipids, we resolved the temporal events taking place in the liver in response to acute HFD exposure in both wild-type and adiponectin-overexpressing mice. Increased levels of adiponectin potently protect against HFD-induced hepatic lipid accumulation and preserve insulin sensitivity. Given these profound effects of adiponectin, we propose that adiponectin is a factor that increases the metabolic flexibility of adipose tissue, enhancing its ability to maintain proper function under metabolically challenging conditions.
代谢健康的个体能够有效地适应营养状态的变化。在这里,我们专注于脂肪细胞衍生的分泌分子脂联素对具有遗传改变的脂联素水平的小鼠模型中脂肪组织的影响。我们发现,较高的脂联素水平增加了对肾上腺素能受体激动剂的脂肪分解作用的敏感性。与此平行,脂联素过表达小鼠在慢性高脂肪饮食(HFD)喂养下还表现出循环脂肪酸清除率增加和皮下脂肪组织扩张增加。这些对 HFD 的适应性变化与脂肪细胞中线粒体密度增加、脂肪细胞体积减小以及通过游离脂肪酸的有效酯化使参与脂质储存的因子的总体转录上调有关。脂联素过表达的生理反应在许多方面类似于慢性暴露于β3 肾上腺素能激动剂治疗的效果,这也导致胰岛素敏感性的改善。此外,我们使用一种新的基于计算机断层扫描的方法来测量肝脏脂质,以确定在野生型和脂联素过表达小鼠中,急性 HFD 暴露后肝脏中发生的时间事件。脂联素水平的增加可强有力地防止 HFD 诱导的肝脂质积累并保持胰岛素敏感性。鉴于脂联素的这些深远影响,我们提出脂联素是增加脂肪组织代谢灵活性的因素,增强了其在代谢挑战条件下维持适当功能的能力。