Hyaluronan in adipogenesis, adipose tissue physiology and systemic metabolism

Abstract

Hyaluronic acid (HA, also known as hyaluronan), is a non-sulfated linear glycosaminoglycan polymer consisting of repeating disaccharide units of d-glucuronic acid and N-acetyl-d-glucosamine abundantly present in the extracellular matrix. The sizes of hyaluronic acid polymers range from 5000 to 20,000,000 Da in vivo, and the functions of HA are largely dictated by its size. Due to its high biocompatibility, HA has been commonly used as soft tissue filler as well as a major component of biomaterial scaffolds in tissue engineering. Several studies have implicated that HA may promote differentiation of adipose tissue derived stem cells in vitro or in vivo when used as a supporting scaffold. However, whether HA actually promotes adipogenesis in vivo and the subsequent metabolic effects of this process are unclear. This review summarizes some recent publications in the field and discusses the possible directions and approaches for future studies, focusing on the role of HA in the adipose tissue.

Keywords: Adipogenesis; Adipose tissue; Dermal filler; Extracellular matrix; Hyaluronan; Hyaluronic acid.

Fig. 1.

Detection of de novo adipogenesis using AdipoChaser mice. (A) Schematic graph of the AdipoChaser system. Adiponectin-rtTA (Adipoq-rtTA), TRE-Cre and Rosa26-loxP-stop-loxP-lacZ triple transgenic mouse is hereby called the AdipoChaser mouse. It constitutively expresses rtTA in mature adipocytes but only expresses Cre when doxycycline (dox) is supplemented. The Cre will subsequently recombine the loxP sites and remove the stop cassette to allow expression of LacZ. The LacZ expression will persist even after removal of dox. But new adipocytes emerging from non-adiponectin expressing progenitor or stem cells after doxycycline removal will not express LacZ. LacZ reacts with X-gal (5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside) and develops a dark blue color. So existing mature adipocytes will be labeled blue after dox supplementation, and any new adipocytes emerging after removal of dox will not be labeled. (B) Representative β-gal (blue) and Perilipin1 (red) staining of subcutaneous white adipose tissue in AdipoChaser mouse 6 weeks after Juvederm injection. Nuclei are counterstained with DAPI (blue). The circle indicates the boundary of Juvederm and adipose tissue. Scale bar: 250 μm.