Provided herein are compositions comprising synthetic lipase-stimulating peptides, and methods of treating hyper-triglyceridemia and other conditions and diseases therewith. In particular, synthetic peptides (AV-peptides) and peptidomimetics (AV-peptidomimetics) are provided that exhibit the lipase-stimulating activity of apoA-V or an enhancement thereof, as well as methods of use thereof. Provided herein are compositions comprising a peptide or polypeptide having less than 100% sequence identity with full length ApoA-V, encompassing a portion with at least 50% sequence identity with AV199-224.
