Towards an Insulin Resistant Adipose Model on a Chip

Area of Science:

• Biomedical Engineering
• Metabolic Disease Research
• Cellular Models

Background:

• Adipose tissue and adipocytes regulate insulin sensitivity and energy homeostasis.
• Insulin resistance (IR) in adipocytes is a precursor to diabetes, but underlying mechanisms are unclear.
• Existing in vitro models lack disease state representation, hindering therapeutic development.

Purpose of the Study:

• To establish an organ-on-chip model of insulin-resistant adipocytes.
• To characterize the insulin signaling pathway and lipid metabolism in this model.
• To validate the model's utility for therapeutic discovery.

Main Methods:

• Primary adipocytes were differentiated and maintained in a microfluidic organ-on-chip device.
• Insulin resistance was induced and characterized by analyzing insulin signaling and lipid metabolism.
• The diabetic drug rosiglitazone was used for validation.

Main Results:

• Confirmed insulin resistance via reduced Akt phosphorylation, Glut4 expression/translocation, and glucose uptake.
• Observed disrupted insulin signaling with decreased lipid accumulation and increased glycerol secretion.
• Rosiglitazone treatment significantly improved insulin sensitivity and fatty acid metabolism.

Conclusions:

• The adipose-on-chip model effectively replicates key characteristics of insulin resistance.
• This model can be utilized for studying diabetes pathogenesis.
• The model facilitates the discovery of novel therapeutics for diabetes.