PLIN1, encoding perilipin-1, is a member of the PAT protein family associated with lipid droplet surface proteins. It coats lipid droplets in adipocytes, playing a vital role in droplet formation, triglyceride storage, and lipolysis. Phosphorylation of PLIN1 is crucial during adipose tissue lipolysis and fat storage in adipocytes. It is also involved in signaling pathways related to fat proliferation and differentiation, such as the AMPK, Wnt, and PPAR pathways [3].

Some studies have investigated the effects of PLIN1 haploinsufficiency. In a large population-based cohort, individuals with PLIN1 protein-truncating variants (PTVs) had a favorable metabolic profile, including increased high-density lipoprotein cholesterol, reduced triglycerides, reduced waist-to-hip ratio, and reduced systolic blood pressure. These individuals also had a reduced risk of myocardial infarction and hypertension [1]. In contrast, pathogenic variants in PLIN1 can cause an autosomal dominant form of familial partial lipodystrophy (FPL) associated with severe insulin resistance, hepatic steatosis, and hypertriglyceridemia. The hypertriglyceridemia in PLIN1-related FPL results from a marked decrease in the catabolism of triglyceride-rich lipoproteins, potentially due to a reduction in lipoprotein lipase (LPL) availability related to decreased adipose tissue mass [2]. In chicken preadipocytes, knockout of PLIN1 decreased differentiation ability and early apoptotic activity, increased proliferation ability, promoted lipolysis under basal conditions, and inhibited lipolysis under hormone stimulation [4].

In conclusion, PLIN1 is essential for lipid metabolism, adipocyte function, and maintaining metabolic homeostasis. Studies on PLIN1, especially through gene knockout models in various organisms, have provided insights into its role in metabolic diseases such as lipodystrophy, insulin resistance, and cardiovascular-related conditions. These findings contribute to understanding the molecular mechanisms underlying these diseases and may guide the development of targeted therapeutic strategies.

References:

1. Patel, Kashyap A, Burman, Shivang, Laver, Thomas W, Frayling, Timothy M, Weedon, Michael N. . PLIN1 Haploinsufficiency Causes a Favorable Metabolic Profile. In The Journal of clinical endocrinology and metabolism, 107, e2318-e2323. doi:10.1210/clinem/dgac104. https://pubmed.ncbi.nlm.nih.gov/35235652/

2. Vergès, Bruno, Vantyghem, Marie-Christine, Reznik, Yves, Capel, Emilie, Vigouroux, Corinne. 2024. Hypertriglyceridemia Results From an Impaired Catabolism of Triglyceride-Rich Lipoproteins in PLIN1-Related Lipodystrophy. In Arteriosclerosis, thrombosis, and vascular biology, 44, 1873-1883. doi:10.1161/ATVBAHA.124.320774. https://pubmed.ncbi.nlm.nih.gov/38899472/

3. Li, Shijun, Raza, Sayed Haidar Abbas, Zhao, Chunping, Cheng, Gong, Zan, Linsen. 2020. Overexpression of PLIN1 Promotes Lipid Metabolism in Bovine Adipocytes. In Animals : an open access journal from MDPI, 10, . doi:10.3390/ani10111944. https://pubmed.ncbi.nlm.nih.gov/33105676/

4. Zhai, Guiying, Pang, Yongjia, Zou, Yichong, Li, Hui, Wang, Yuxiang. 2022. Effects of PLIN1 Gene Knockout on the Proliferation, Apoptosis, Differentiation and Lipolysis of Chicken Preadipocytes. In Animals : an open access journal from MDPI, 13, . doi:10.3390/ani13010092. https://pubmed.ncbi.nlm.nih.gov/36611701/