Microfluidic systems for studying dynamic function of adipocytes and adipose tissue

Abstract

Recent breakthroughs in organ-on-a-chip and related technologies have highlighted the extraordinary potential for microfluidics to not only make lasting impacts in the understanding of biological systems but also to create new and important in vitro culture platforms. Adipose tissue (fat), in particular, is one that should be amenable to microfluidic mimics of its microenvironment. While the tissue was traditionally considered important only for energy storage, it is now understood to be an integral part of the endocrine system that secretes hormones and responds to various stimuli. As such, adipocyte function is central to the understanding of pathological conditions such as obesity, diabetes, and metabolic syndrome. Despite the importance of the tissue, only recently have significant strides been made in studying dynamic function of adipocytes or adipose tissues on microfluidic devices. In this critical review, we highlight new developments in the special class of microfluidic systems aimed at culture and interrogation of adipose tissue, a sub-field of microfluidics that we contend is only in its infancy. We close by reflecting on these studies as we forecast a promising future, where microfluidic technologies should be capable of mimicking the adipose tissue microenvironment and provide novel insights into its physiological roles in the normal and diseased states. Graphical abstract This critical review focuses on recent developments and challenges in applying microfluidic systems to the culture and analysis of adipocytes and adipose tissue.

Keywords: Adipocyte; Adipokine; Batokine; Bioanalytical methods; Hormone; Microfluidics microfabrication.

Fig. 1

Recent examples of microfluidic systems for studying dynamic function of adipocytes and adipose tissue. (A) Schematic of microfluidic device for 3T3-L1 adipocyte stimulation and sampling, coupled to solid phase extraction and mass spectrometry (SPE-MS), for monitoring non-esterified fatty acid (NEFA) secretion profiles from adipocytes [49]. (B) Average NEFA secretion profiles during basal and isoproterenol/forskolin stimulation of adipocytes using the chip in (A) for stimulation and sampling. (C) On-chip culture systems for primary adipose tissue [42]. Primary mouse adipocytes were cultured in a 3D collagen matrix (top left) on an 8-channel microfluidic sampling device. Alternatively, explants were trapped using customized traps. 3D CAD rendering (top right) is shown with 3D-printed explant traps (middle right). (D) Temporal program of combined insulin, glucose, and fatty acid inputs to adipose explants using a microfluidic multiplexer (μMUX) device [39]. (E) Real-time fatty acid uptake responses from treatments in (D) showed insulin-dependent exchange rates. (F) Representative fluorescent images of on-chip explants used to generate data in (E). (G) Compiled data from (E) showed insulin-dependent fatty acid exchange dynamics. (H) Assignment map of the programmable, automated μMUX device, showing the 10 required input channels and one output waste channel used for (D)–(G). Reproduced from references , , and with permission from the Royal Society of Chemistry and from Springer Publishing Company