In fact, berberine exerts its action both systemically and at the liver level; it can therefore be argued that the free plasma fraction is representative of the systemic action (such as hormones and insulin resistance), while the conjugated fraction (where total represents the sum of free and conjugated) may exert its relevant metabolic activity in the liver (AMPK, PCSK9, and lipidic metabolism). The gene discussed is PCSK9; the disease is Insulin resistance.