4‐HNE Unfavorably Alters Muscle Mitochondrial Bioenergetics and Cell Viability

Abstract

Linoleic acid consumption has increased by orders of magnitude over the past century, eliciting an increasing awareness of and appreciation for its metabolites, particularly 4‐hydroxynonenal (4‐HNE). Elevated 4‐HNE formation is causally implicated in myriad neurodegenerative, cardiovascular, autoimmune, and metabolic disorders. The purpose of this project was to identify the effect of 4‐HNE on muscle cell mitochondrial bioenergetics. Our primary observation was that physiological levels of 4‐HNE compromised muscle cell mitochondrial oxygen consumption, leading to reduced oxygen flux despite a substantial production of reactive oxygen species (ROS). Indeed, when viewed in light of the reduced oxygen consumption, the relative production of ROS with 4‐HNE was even more pronounced. These findings could explain the significant reduction of cell viability demonstrated. In conclusion, this work joins the growing body of evidence suggesting a need to scrutinize dietary linoleic acid consumption.