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Rethinking the ethics of research involving nonhuman animals: Introduction

机译：重新思考涉及非人类动物的研究伦理：简介

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PURPOSE OF REVIEW: We summarize recent mechanistic and physiological studies related to the role of perilipin 5 (Plin5) in regulating lipid droplet accumulation and protection to fatty acids in tissues with high lipid oxidative metabolism. RECENT FINDINGS: Plin5 is a lipid droplet targeting protein that promotes association of lipid droplets with mitochondria and is most highly expressed in oxidative tissues, including cardiac and skeletal muscle. Recent in-vivo and in-vitro data indicate an important role for Plin5 in the regulation of cardiac lipid storage and function. Targeted overexpression of Plin5 in heart causes steatosis, mild mitochondria dysfunction, and hypertrophy in cardiac tissue, but without affecting cardiac function. In contrast, whole body ablation of Plin5 (Plin5a?? mice) reduces cardiac lipid droplet formation, increases cardiac fatty acid oxidation, and promotes cardiac dysfunction; cardiac defects can be prevented with antioxidative therapy. These data suggest a cytoprotective role for Plin5 to promote lipid storage but to limit fatty acid toxicity, parameters critical for tissues with high lipid oxidative metabolism. SUMMARY: In-vivo and in-vitro data suggest that Plin5 is part of a cell-adaptive response to high lipid oxidative metabolism to protect lipid droplet storage against neutral lipases and, so, limit fatty acid accumulation. Although the specific mechanisms that underlie Plin5 lipid droplet storage protection in oxidative tissues remain to be fully elucidated, Plin5 provides a basis for the novel cytoprotective nature of lipid droplets.
机译：审查的目的：我们总结了最近的机制和生理学研究，与periplipin 5（Plin5）在调节脂质氧化代谢高的组织中调节脂质小滴的积累和保护脂肪酸的作用有关。最近的发现：Plin5是一种脂质滴靶向蛋白，可促进脂质滴与线粒体的缔合，并在包括心脏和骨骼肌在内的氧化组织中高度表达。最近的体内和体外数据表明，Plin5在调节心脏脂质储存和功能中起着重要作用。心脏中Plin5的靶向过度表达可导致脂肪变性，轻度线粒体功能障碍和心脏组织肥大，但不会影响心脏功能。相反，Plin5（Plin5aβ小鼠）的全身消融减少了心脏脂质液滴的形成，增加了心脏脂肪酸的氧化，并促进了心脏功能障碍。可以通过抗氧化疗法预防心脏缺陷。这些数据表明Plin5具有细胞保护作用，可促进脂质存储，但可限制脂肪酸毒性，这对具有高脂质氧化代谢的组织至关重要。摘要：体内和体外数据表明，Plin5是对高脂质氧化代谢的细胞适应性反应的一部分，以保护脂质液滴储存免受中性脂肪酶的侵害，从而限制了脂肪酸的积累。尽管仍然需要充分阐明在氧化组织中Plin5脂质小滴储存保护基础的具体机制，但Plin5为脂质小滴的新型细胞保护性质提供了基础。

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