title: A multiscale modeling framework for studying the mechanobiology of sarcopenic obesity.
abstract: An inactive sedentary lifestyle is a common risk factor contributing to sarcopenic obesity. At the cell scale, sustained mechanical deformations of the plasma membrane (PM) in adipocytes, characterizing chronic static loading in weight-bearing tissues during prolonged sitting or lying, were found to promote adipogenesis. Taking a mechanobiological perspective, we correlated here the macroscale mechanical deformations of weight-bearing adipose tissues (subcutaneous and intramuscular) with mechanical strains developing in the PMs of differentiating adipocytes. An innovative multiscale modeling framework for adipose tissues was developed for this purpose, where the buttocks, adipose tissues, adipocytes and the subcellular components: intracytoplasmic nucleus and lipid droplets as well as the PMs of the cells, were all represented. We found that a positive feedback loop very likely exists and is involved in the onset and progression of sarcopenic obesity, as follows. Adipogenesis in statically deformed adipocytes results in gaining more macroscopic subcutaneous and intramuscular fat mass, which then increases fat deformations macroscopically and microscopically, and hence triggers additional adipogenesis, and so on. Our present study is highly relevant in research of sarcopenic obesity and other adipose-related diseases such as diabetes, since mechanical distortion of adipocytes promotes adipogenesis and fat gain at the different dimensional scales.
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, 69978, Tel Aviv, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Shoham
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, 69978, Tel Aviv, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Levy
authors.affiliation: Department of Radiology, Haemek Medical Center, Afula, Israel.|Department of Radiology, Hospital of University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Nogah
authors.initials: N
authors.lastname: Shabshin
authors.affiliation: Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Dafna
authors.initials: D
authors.lastname: Benayahu
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, 69978, Tel Aviv, Israel. gefen@eng.tau.ac.il.
authors.forename: Amit
authors.initials: A
authors.lastname: Gefen
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology / Q000503:physiopathology; D001696:Biomechanical Phenomena; D006801:Humans; D008954:Models, Biological; D009765:Obesity / Q000503:physiopathology*
keywords: Adipogenesis; Adipose tissue; Finite element model; Mechanotransduction