Need a deeper understanding of fat metabolism? This review delves into the intricacies of peroxisomal β-oxidation and the role of peroxisome proliferator–activated receptor α (PPARα) as an adaptive metabolic system. Mitochondria catalyze the β-oxidation of the bulk of short-, medium-, and long-chain fatty acids derived from diet, and this pathway constitutes the major process by which fatty acids are oxidized to generate energy. Peroxisomes are involved in the β-oxidation chain shortening of long-chain and very-long-chain fatty acyl-coenzyme (CoAs). Long-chain and very-long-chain fatty acids (VLCFAs) are also metabolized by the cytochrome P450 CYP4A ω-oxidation system to dicarboxylic acids that serve as substrates for peroxisomal β-oxidation. The peroxisomal β-oxidation system consists of a classical peroxisome proliferator–inducible pathway and a second noninducible pathway. Genes encoding the classical β-oxidation pathway are transcriptionally regulated by PPARα. Evidence from mice deficient in PPARα and peroxisomal enzymes highlights the critical importance of PPARα and peroxisomal fatty acyl-CoA oxidase in energy metabolism, and in the development of hepatic steatosis, steatohepatitis, and liver cancer.
Published in the Annual Review of Nutrition, this article is appropriately contextualized within the journal's dedication to research concerning all nutritional aspects and how they impact people's health. By detailing the intricacies of peroxisomal β-oxidation and PPARα, it aligns with the journal's focus on understanding the molecular mechanisms underpinning nutrition and metabolism.