Fatty Acid Oxidation and Cardiovascular Risk during Menopause: A Mitochondrial Connection?

Figure 3

General scheme of the hypothesis raised by the present paper. It is proposed that menopause, as a condition natural to the normal aging process, is accompanied by specific mitochondrial alterations (bottom red box, arrow with a dark cloud) which decrease their ability to cope with an increased flux of long-chain fatty acyl CoA, resulting from augmented plasma levels. Inability to process fatty acyl CoA may result in accumulation of fatty acid intermediates including tri- and diacylglycerol, as well as ceramide, which causes myocardial lipotoxicity and may even result into activation of apoptotic signaling. The cardiovascular risk increases under these circumstances, which is fueled by other coexisting pathological conditions or by pharmacological interventions that present toxicity to the cardiovascular system. Estradiol (represented by green arrows) has been proposed to increase fatty acid oxidation by mitochondria, decreasing the flux through other biosynthetic pathways, preventing the potential accumulation of deleterious metabolites and increasing fatty acid-derived mitochondrial ATP production.