The use of three-dimensional primary human myospheres to explore skeletal muscle effects of in vivo krill oil supplementation

• DOI: 10.1007/s44164-025-00087-6
• Publication Date: 2025-04-30T08:19:45Z
• Authors: Andrea Dalmao-Fer...; Parmeshwar B. Katare; Hege G. Bakke; Håvard Hamarsland; Stian Ellefsen; Sachin Singh; Tuula Anneli Nyman; Eili Tranheim Kase; Arild C. Rustan; G. Hege Thoresen
• Keywords: Primary (astronomy)

Abstract

Purpose Supplementation with krill oil has shown effects on whole-body lipid and glucose metabolism, as well as on skeletal muscle strength and function. We previously showed that krill oil intervention in vivo promoted fatty acid metabolism and protein synthesis in cultured human myotubes in a two-dimensional (2D) model. The aim of this study was to explore the effects of krill oil supplementation in vivo in a 3D myosphere model, and to compare a the human skeletal muscle 3D cell model to a 2D model.

Methods Myospheres were formed from myoblasts obtained before and after 7 weeks of in vivo krill oil intervention. Glucose and oleic acid metabolism were assessed, and transcriptomic and proteomic analyses were performed.

Results In vivo intervention with krill oil increased glucose metabolism in myospheres, while no effect was observed on fatty acid metabolism. Transcriptomic analyses of myospheres after krill oil intervention showed increased expression of genes involved in pathways like motor proteins and hypertrophy, as well as in calcium signaling, of which motor proteins and hypertrophy pathways have not been described in 2D myotube cultures. Proteomic analyses after krill oil intervention showed increased expression of proteins in glycolysis/gluconeogenesis and fatty acid degradation. Comparison of proteins expressed in the 3D myosphere model and the 2D myotube model at the basal level showed that in myospheres, mitochondrial gene expression and translation dominated, while in 2D cultures, mitochondrial organization and response to oxidative stress were more important.

Conclusion These findings suggest that in vivo krill oil intervention induces different metabolic effects when comparing 3D and 2D cultures. In contrast to the 2D model, data obtained with the 3D model showed gene expression changes that are more compatible with previously observed results in vivo concerning skeletal muscle motoric function. Hence, the 3D cell model might better reflect krill oil-induced modifications in skeletal muscle performance in vivo than the 2D model.