In individuals with obesity and/or type 2 diabetes, niacin infusion reduces fasting phosphorylation of Akt at Ser473/474 and perilipin 1 at Ser552 in adipose tissue compared to saline infusion, indicating that niacin impairs key signaling nodes involved in lipolysis suppression despite its overall antilipolytic effect.

Niacin blocks the activation of two key proteins in fat cells that normally stop fat breakdown, even though it still reduces fat release overall. This happens because the fat cells have a broken control system that can't respond properly to signals meant to shut down fat breakdown, so the proteins that physically block fat enzymes stay inactive, allowing fat to leak out despite the signal to stop.