Generation of functional fat organoid from rat superficial fascia

Abstract

ABSTRACT The organoid is a 3D cell architecture formed by self-organized tissues or cells in vitro with similar cell types, histological structures, and biological functions of the native organ. Depending on the unique organ structures and cell types, producing organoids requires individualized design and is still challenging. Organoids of some tissues, including adipose tissue, remain to generate to be more faithful to their original organ in structure and function. We previously established a new model of the origin of adipose cells originating from non-adipose fascia tissue. Here, we investigated superficial fascia fragments in 3D hydrogel and found they were able to transform into relatively large adipocyte aggregates containing mature unilocular adipocytes, which were virtually “fat organoids”. Such fascia-originated fat organoids had a typical structure of adipose tissues and possessed the principal function of adipose cells in the synthesis, storage, hydrolysis of triglycerides and adipokines secretion. Producing fat organoids from superficial fascia can provide a new approach for adipocyte research and strongly evidences that both adipose tissues and cells originate from fascia. Our findings give insights into metabolic regulation by the crosstalk between different organs and tissues and provide new knowledge for investigating novel treatments for obesity, diabetes and other metabolic diseases. Abbreviations: 3D: three dimensional; ASC: adipose-derived stromal cells; C/EBP: CCAAT-enhancer-binding protein; EdU: 5-ethynyl-2-deoxyuridine; FABP4: fatty acid-binding protein 4; FAS: fatty acid synthase; FSCs: fascia-derived stromal cells; Plin1: perilipin-1; Plin2: perilipin-2; PPARγ: peroxisome proliferator-activated receptor γ; WAT: white adipose tissue