Plin5, also known as perilipin 5, is a protein that coats lipid droplets (LDs) in cardiomyocytes and other oxidative tissues. It plays a crucial role in lipid metabolism, regulating the trafficking of fatty acids (FAs) between LDs and mitochondria, and maintaining a balance between lipid storage and utilization. Plin5 is involved in multiple pathways, such as the SIRT1/PGC-1α/PPARα-dependent pathway related to mitochondrial biogenesis and oxidative metabolism [1]. Its study using genetic models like knockout (KO) mouse models can help uncover its function in normal physiological and disease conditions.

In KO mouse models, Plin5-deficient cardiomyocytes store fewer LDs, mainly by repressing adipose triglyceride lipase activity without changing fatty acid oxidation capacity [4]. Hepatic PLIN5 deficiency impairs lipogenesis through mitochondrial dysfunction, indicating its role in mediating the interaction between LDs and mitochondria [3]. In vascular smooth muscle cells, Plin5 knockdown leads to accelerated neointima hyperplasia, excessive cell proliferation and migration, suggesting its inhibitory role in these processes by interacting with PGC-1α [5].

In summary, Plin5 is essential for regulating lipid metabolism, including FA trafficking between LDs and mitochondria, and lipogenesis. KO mouse models have revealed its significance in diseases such as diabetic cardiomyopathy, where it may be involved in processes like lipotoxicity and ferroptosis [2], as well as in vascular disorders like neointima hyperplasia. Understanding Plin5's function provides insights into the mechanisms of these diseases and potential therapeutic targets.

References:

1. Najt, Charles P, Khan, Salmaan A, Heden, Timothy D, Chow, Lisa S, Mashek, Douglas G. 2019. Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1. In Molecular cell, 77, 810-824.e8. doi:10.1016/j.molcel.2019.12.003. https://pubmed.ncbi.nlm.nih.gov/31901447/

2. Shen, Xiaoyu, Zhang, Jiamei, Zhou, Zhou, Yu, Ruiqun. 2024. PLIN5 Suppresses Lipotoxicity and Ferroptosis in Cardiomyocyte via Modulating PIR/NF-κB Axis. In International heart journal, 65, 537-547. doi:10.1536/ihj.24-002. https://pubmed.ncbi.nlm.nih.gov/38749744/

3. Zhang, Enxiang. 2022. Hepatic PLIN5 Deficiency Impairs Lipogenesis through Mitochondrial Dysfunction. In International journal of molecular sciences, 23, . doi:10.3390/ijms232415598. https://pubmed.ncbi.nlm.nih.gov/36555245/

4. Li, Yuchuan, Torp, May-Kristin, Norheim, Frode, Vaage, Jarle, Dalen, Knut Tomas. 2020. Isolated Plin5-deficient cardiomyocytes store less lipid droplets than normal, but without increased sensitivity to hypoxia. In Biochimica et biophysica acta. Molecular and cell biology of lipids, 1866, 158873. doi:10.1016/j.bbalip.2020.158873. https://pubmed.ncbi.nlm.nih.gov/33373698/

5. Gan, Xueqing, Zhao, Jiaqi, Chen, Yingmei, Yang, Dachun, Sun, Xiongshan. . Plin5 inhibits proliferation and migration of vascular smooth muscle cell through interacting with PGC-1α following vascular injury. In Bioengineered, 13, 10665-10678. doi:10.1080/21655979.2022.2065762. https://pubmed.ncbi.nlm.nih.gov/35470759/