Thrombin-Mediated Formation of Globular Adiponectin Promotes an Increase in Adipose Tissue Mass.

Autor: Zahradka P; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.; Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.; Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada., Taylor CG; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.; Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.; Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada., Tworek L; Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada., Perrault R; Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada., M'Seffar S; Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada., Murali M; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.; Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada., Loader T; Canadian Centre for Agri-food Research in Health and Medicine, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada., Wigle JT; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.; Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada.
Jazyk: angličtina
Zdroj: Biomolecules [Biomolecules] 2022 Dec 23; Vol. 13 (1). Date of Electronic Publication: 2022 Dec 23.
DOI: 10.3390/biom13010030
Abstrakt: A decrease in the circulating levels of adiponectin in obesity increases the risk of metabolic complications, but the role of globular adiponectin, a truncated form produced by proteolytic cleavage, has not been defined. The objective of this investigation was to determine how globular adiponectin is generated and to determine whether this process impacts obesity. The cleavage of recombinant full-length adiponectin into globular adiponectin by plasma in vitro was used to identify Gly-93 as the N-terminal residue after proteolytic processing. The amino acid sequence of the cleavage site suggested thrombin was the protease responsible for cleavage, and inhibitors confirmed its likely involvement. The proteolytic site was modified, and this thrombin-resistant mutant protein was infused for 4 weeks into obese adiponectin-knockout mice that had been on a high-fat diet for 8 weeks. The mutation of the cleavage site ensured that globular adiponectin was not generated, and thus did not confound the actions of the full-length adiponectin. Mice infused with the mutant adiponectin accumulated less fat and had smaller adipocytes compared to mice treated with globular adiponectin, and concurrently had elevated fasting glucose. The data demonstrate that generation of globular adiponectin through the action of thrombin increases both adipose tissue mass and adipocyte size, but it has no effect on fasting glucose levels in the context of obesity.
Databáze: MEDLINE
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