Paper

Adipose cells and tissues soften with lipid accumulation while in diabetes adipose tissue stiffens

Schluessler, Raimund, Tschoep, Matthias, Guck, Jochen, Mueller, Torsten, Brankatschk, Marko, Harger, Alexandra, Wabitsch, Martin, Kim, Kyoohyun, Braun, Juergen, Taubenberger, Anna Verena, Angela Ariza Schellenberger, Kotzbeck, Petra, Joan-Carles Escolano, Stemmer, Kerstin, Sack, Ingolf, Abuhattum, Shada

2022

Overview

Adipose tissue expansion involves both differentiation of new precursors and size increase of mature adipocytes. While the two processes are well balanced in healthy tissues, obesity and diabetes type II are associated with abnormally enlarged adipocytes and excess lipid accumulation. We hypothesised that adipocyte shape and size changes with differentiation and lipid accumulation would be accompanied by changes in the mechanical phenotype at both the cell and tissue level. We quantified by optical diffraction tomography (ODT) that differentiating preadipocytes increased their volumes drastically. Atomic force microscopy (AFM)-indentation and -microrheology revealed that during the early phase of differentiation, human preadipocytes became more compliant and more fluid-like, concomitant with ROCK-mediated F-actin remodelling. Adipocytes that had accumulated large lipid droplets were more compliant, and further promoting lipid accumulation led to an even more compliant phenotype. In line with that, high fat diet-induced obesity was associated with more compliant adipose tissue compared to lean animals, both for drosophila fat bodies and murine gonadal adipose tissue. In contrast, adipose tissue of diabetic mice became significantly stiffer as shown not only by AFM but also magnetic resonance elastography (MRE). Altogether, we dissect relative contributions of the cytoskeleton and lipid droplets to cell and tissue mechanical changes across different functional states, such as differentiation, nutritional state and disease. Since preadipocytes are mechanosensitive, tissue stiffening in diabetes might be critical to the balance between hyperplasia and hypertrophy and moreover present a potential target in the prevention of metabolic disorders. Competing Interest Statement T.M. is employed by the Bruker BioAFM GmbH. M.H.T. is a member of the scientific advisory board of ERX Pharmaceuticals, Cambridge, MA, USA; was a member of the Research Cluster Advisory Panel (ReCAP) of the Novo Nordisk Foundation between 2017 and 2019; attended a scientific advisory board meeting of the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, in 2016; received funding for his research projects from Novo Nordisk (2016-2020) and Sanofi-Aventis (2012-2019); was a consultant for Bionorica SE (2013-2017), Menarini Ricerche S.p.A. (2016) and Bayer Pharma AG Berlin (2016); and, as former Director of the Helmholtz Diabetes Center and the Institute for Diabetes and Obesity at Helmholtz Zentrum Muenchen (2011-2018), and, since 2018, as CEO of Helmholtz Zentrum Muenchen, has been responsible for collaborations with a multitude of companies and institutions worldwide - in this capacity, he discussed potential projects with and has signed/signs contracts for his institute(s) and for the staff for research funding and/or collaborations with industry and academia worldwide, including but not limited to pharmaceutical corporations such as Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medigene, Arbormed, BioSyngen and others; in this role, was/is further responsible for commercial technology transfer activities of his institute(s), including diabetes-related patent portfolios of Helmholtz Zentrum Muenchen as, for example, WO/2016/188932 A2 or WO/2017/194499 A1; and confirms that, to the best of his knowledge, none of the above funding sources were involved in the preparation of this paper. Other authors do not have any conflict of interest.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Actin / Adipocytes / Adipose tissue / Atomic force microscopy / Biophysics / Body fat / Cytoskeleton / Diabetes / Diabetes mellitus / Funding / High fat diet / Hyperplasia / Hypertrophy / Lipids / Metabolic disorders / Metabolism / Obesity / Phenotypes / Preadipocytes