The response to fasting and refeeding reveals functional regulation of lipoprotein lipase proteoforms

Frontiers in Physiology

Physiology

Montserrat Carrascal¹  Joaquin Abian¹  M. Dolores López-Tejero²  Pere Carulla²  David Ricart-Jané²  Miquel Llobera²  Albert Casanovas²  Míriam Badia-Villanueva²  Sergi Civit³ 

[1] Biological and Environmental Proteomics, Institute of Biomedical Research of Barcelona, Spanish National Research Council, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IIBB-CSIC/IDIBAPS), Barcelona, Spain;Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Spain;Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Spain;

关键词: lipid metabolism;    lipoprotein lipase;    proteoform;    tissue-specific regulation;    fasting;    white adipose tissue;    2D electrophoresis;   

DOI  :  10.3389/fphys.2023.1271149

 received in 2023-08-01, accepted in 2023-10-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

Lipoprotein lipase (LPL) is responsible for the intravascular catabolism of triglyceride-rich lipoproteins and plays a central role in whole-body energy balance and lipid homeostasis. As such, LPL is subject to tissue-specific regulation in different physiological conditions, but the mechanisms of this regulation remain incompletely characterized. Previous work revealed that LPL comprises a set of proteoforms with different isoelectric points, but their regulation and functional significance have not been studied thus far. Here we studied the distribution of LPL proteoforms in different rat tissues and their regulation under physiological conditions. First, analysis by two-dimensional electrophoresis and Western blot showed different patterns of LPL proteoforms (i.e., different pI or relative abundance of LPL proteoforms) in different rat tissues under basal conditions, which could be related to the tissue-specific regulation of the enzyme. Next, the comparison of LPL proteoforms from heart and brown adipose tissue between adults and 15-day-old rat pups, two conditions with minimal regulation of LPL in these tissues, yielded virtually the same tissue-specific patterns of LPL proteoforms. In contrast, the pronounced downregulation of LPL activity observed in white adipose tissue during fasting is accompanied by a prominent reconfiguration of the LPL proteoform pattern. Furthermore, refeeding reverts this downregulation of LPL activity and restores the pattern of LPL proteoforms in this tissue. Importantly, this reversible proteoform-specific regulation during fasting and refeeding indicates that LPL proteoforms are functionally diverse. Further investigation of potential differences in the functional properties of LPL proteoforms showed that all proteoforms exhibit lipolytic activity and have similar heparin-binding affinity, although other functional aspects remain to be investigated. Overall, this study demonstrates the ubiquity, differential distribution and specific regulation of LPL proteoforms in rat tissues and underscores the need to consider the existence of LPL proteoforms for a complete understanding of LPL regulation under physiological conditions.

【 授权许可】

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Copyright © 2023 Carulla, Badia-Villanueva, Civit, Carrascal, Abian, Ricart-Jané, Llobera, Casanovas and López-Tejero.