Inflammation
PPARgamma suppresses IL-6-driven Lp(a) production in liver cells, and the diabetes drug pioglitazone can trigger that suppression (J Cardiovasc Pharmacol 2024)
Original title: Peroxisome Proliferator-Activated Receptor Gamma Regulates Interleukin-6-Induced Lipoprotein (a) Gene Expression in Human HepG2 Cells
Using human HepG2 liver cells, the authors investigated how interleukin-6 (IL-6), a cytokine known to raise Lp(a) via a responsive binding site in the LPA gene promoter, interacts with peroxisome proliferator-activated receptor gamma (PPARgamma) to regulate hepatic Lp(a) synthesis. Genetic mapping identified a regulatory LPA promoter variant overlapping a PPARgamma binding site. Knocking down PPARgamma heightened IL-6-mediated LPA gene transcription, while pioglitazone, a PPARgamma agonist already used to treat type 2 diabetes, suppressed it. The findings establish PPARgamma as a negative regulator of inflammation-driven hepatic Lp(a) production and raise the possibility that PPARgamma agonists such as pioglitazone could be repurposed to blunt Lp(a) elevation in patients with inflammatory conditions, though this remains an in vitro finding requiring clinical validation.
Original abstract
Lipoprotein(a) [Lp(a)] is a risk factor for coronary disease. Although levels are primarily genetically determined, data from patients with inflammatory diseases indicate that the inflammatory milieu is associated with increased Lp(a) levels. Lp(a) is synthesized in the liver and the LPA gene promoter contains an interleukin-6 (IL-6) responsive binding site, but the regulatory steps linking inflammation with hepatic Lp(a) synthesis are not well clarified. We explored the interplay between IL-6, peroxisome proliferator-activated receptor gamma (PPARγ), and Lp(a) synthesis in HepG2 cells. Through genetic mapping, a regulatory variant within the LPA promoter overlapping with a PPARγ binding site was identified. In in vitro experiments, IL-6-mediated LPA gene transcription was heightened with PPARγ knock-down and suppressed with pioglitazone, a PPARγ agonist. These results demonstrate an important role of PPARγ as a negative regulator of IL-6-induced hepatic Lp(a) production and may represent a new therapeutic target for patients with inflammatory conditions characterized by elevated Lp(a).
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.