α-Lipoic Acid Improves Hepatic Metabolic Dysfunctions in Acute Intermittent Porphyria: A Proof-of-Concept Study.

ABSTRACT: Acute intermittent porphyria (AIP) is caused by the haploinsufficiency of porphobilinogen deaminase (PBGD) enzymatic activity. Acute attacks occur in response to fasting, and alterations in glucose metabolism, insulin resistance, and mitochondrial turnover may be involved in AIP pathophysiology. Therefore, we investigated the metabolic pathways in PBGD-silenced hepatocytes and assessed the efficacy of an insulin mimic, α-lipoic acid (α-LA), as a potential therapeutic strategy. HepG2 cells were transfected with siRNA-targeting PBGD (siPBGD). Cells were cultured with low glucose concentration to mimic fasting and exposed to α-LA alone or with glucose. At baseline, siPBGD cells showed a lower expression of genes involved in glycolysis and mitochondrial dynamics along with reduced total ATP le

SUBMITTER: Longo M 

PROVIDER: S-EPMC8468570 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature