Lpl-KO Mouse

Lpl, or lipoprotein lipase, is a critical enzyme in humans. It hydrolyzes triglycerides from the cores of lipoproteins circulating in plasma, playing a key role in lipid metabolism. It also interacts with receptors to mediate lipoprotein uptake, directing lipid distribution via catalytic and non-catalytic functions, and is essential for providing fuel to peripheral tissues [2]. The regulation of Lpl is tissue-dependent and nutritionally responsive, and it is involved in pathways related to lipid homeostasis [2]. Genetic models, such as knockout mouse models, are valuable for studying Lpl.

Gpihbp1 knockout mice, which lack a protein important for Lpl function, develop severe hypertriglyceridemia (HTG) after weaning. Suckling Gpihbp1-/-mice with high hepatic Lpl expression do not develop HTG, while Gpihbp1-/-rat pups without hepatic Lpl expression do. Adeno-associated virus (AAV)-mediated liver-targeted Lpl expression dose-dependently decreases plasma TG levels in Gpihbp1-/-mice and rats, increases post-heparin plasma Lpl mass and activity, decreases mortality in Gpihbp1-/-rat pups, and reduces susceptibility and severity of HTG-related acute pancreatitis (HTG-AP). However, muscle expression of AAV-Lpl has no significant effect on HTG [1]. In addition, in Gpihbp1-/-mice housed at 30 °C, ANGPTL4, which increases in brown adipose tissue (BAT) at this temperature, leads to a decrease in Lpl levels within the interstitial spaces of BAT, showing that ANGPTL4 regulates Lpl levels before its transport into capillaries [3].

In conclusion, Lpl is essential for lipid metabolism, especially in the hydrolysis of plasma triglycerides. Studies using Gpihbp1 knockout mouse models have revealed that Lpl expression, particularly in the liver, can significantly impact the development of HTG and HTG-AP. These models also show the importance of regulatory proteins like ANGPTL4 in controlling Lpl levels, contributing to our understanding of lipid-related disease mechanisms [1,3].

References:

1. Yuan, Chenchen, Xu, Yao, Lu, Guotao, Li, Baiqiang, Li, Weiqin. 2023. AAV-mediated hepatic LPL expression ameliorates severe hypertriglyceridemia and acute pancreatitis in Gpihbp1 deficient mice and rats. In Molecular therapy : the journal of the American Society of Gene Therapy, 32, 59-73. doi:10.1016/j.ymthe.2023.11.018. https://pubmed.ncbi.nlm.nih.gov/37974401/

2. Wheless, Anna, Gunn, Kathryn H, Neher, Saskia B. . Macromolecular Interactions of Lipoprotein Lipase (LPL). In Sub-cellular biochemistry, 104, 139-179. doi:10.1007/978-3-031-58843-3_8. https://pubmed.ncbi.nlm.nih.gov/38963487/

3. Song, Wenxin, Yang, Ye, Heizer, Patrick, Young, Stephen G, Fong, Loren G. 2023. Intracapillary LPL levels in brown adipose tissue, visualized with an antibody-based approach, are regulated by ANGPTL4 at thermoneutral temperatures. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2219833120. doi:10.1073/pnas.2219833120. https://pubmed.ncbi.nlm.nih.gov/36787365/