Infiltration of immune cells into adipose tissue is associated with chronic low-grade inflammation in obese
individuals. To better understand the crosstalk between immune cells and adipocytes, in vivo-like in vitro
models are required. Conventionally transwell culture plates are used for studying the adipocyte–immune
cell interaction; however, the static culture nature of this approach falls short of closely recapitulating the
physiological environment. Here we present a compartmentalized microfluidic co-culture system which
provides a constant-rate of nutrient supply as well as waste removal, resembling the microvascular networks
of the in vivo environment. Human adipocytes and U937 cells were co-cultured in close proximity in
an enclosed system. The porous barrier between the adjacent compartments comprises an array of microchannels, which enables paracrine interaction between cells in adjacent compartments and improved
perfusion-based long term cell feeding. Human pre-adipocytes were fully differentiated into adipocytes on
the chip and remained viable for several weeks. Upon co-culturing with immune cells, adipocytes showed
a tendency to develop insulin resistance. The immune-metabolic correlation has been studied by monitoring
adiponectin and IL-6 expression, as well as glucose uptake upon treatment with insulin. Our microfluidic
system can be potentially used to develop physiologically relevant adipose tissue models to study obesity-associated diseases such as insulin resistance and type 2 diabetes and therefore, facilitate drug development to treat these diseases.