Figure 7.

Possible effects of metreleptin therapy on lipid metabolism in patients with lipodystrophy. Schematic representation of lipoprotein particles identified by NMR, arranged by diameter and density. Small, medium, and large (S, M, L) HDLPs are shown in blue; small, medium, and large (S, M, L) LDLPs in yellow; and very small, small, medium, large, and very large (VS, S, M, L, VL) TRLPs in green. Known effects of metreleptin are indicated with red arrows. Metreleptin lowers TRLPs through multiple mechanisms. Metreleptin decreases food intake [23], which probably decreases chylomicrons. It decreases angiopoietin-like protein 3 (ANGPTL3) [24], which should LPL activity, resulting in increased catabolism of TRLPs and chylomicrons. It also decreases transcription factors involved in de novo lipogenesis [25], which should decrease VLDL production. Metreleptin decreases LDLs via decreased proprotein convertase subtilisin/kexin type 9 (PCSK9) [26]. NEFA, nonesterified fatty acids.