In adults with upper-body obesity and/or type 2 diabetes, the suppression of adipose tissue lipolysis by insulin and niacin is not mediated by differences in proximal signaling proteins such as Akt, but is potentially attributable to shared dysfunction in distal regulators including perilipin 1, indicating a unified defect in lipolysis control beyond insulin resistance.

In people with upper-body obesity or type 2 diabetes, fat cells cannot properly stop breaking down stored fat when insulin or niacin signals them to do so. This happens because a key protein called perilipin 1, which normally acts like a lock on fat droplets, does not respond correctly to these signals. Even though insulin and niacin start their signals in different ways, both need perilipin 1 to shut off fat breakdown. In these individuals, perilipin 1 remains in a state that keeps the fat droplets open, so fat keeps leaking out regardless of the signal.