Figure 1. Controlling insulin secretion via the adipose tissue-islet connection. Lipids derived from ingested nutrients are metabolized to fatty acids that trigger an intestine-brain-liver neural circuit, which ultimately reduces liver glucose output (blue pathway). New work from Lo et al. suggests that an adipose tissue-islet connection may also help regulate liver glucose output (red pathway).

The authors propose that adipsin (complement factor D; CFD) secreted from adipose tissue produces complement 3a (C3a) that acts remotely at the islets of Langerhans, where b cells reside, to stimulate insulin secretion and ultimately reduce liver glucose output. Whether adipsin would compete with glucagon-like peptide-1 (GLP-1) analogs or work in combination to produce additive effects on insulin secretion remains to be seen.