Mitochondrial Dysfunction in Metabolic Syndrome and Asthma

Figure 2

Overlapping mitochondrial features between metabolic syndrome and asthma. A possible role of mitochondria in the pathogenesis and therapeutics of obese-asthma. Common factors between metabolic syndrome and asthma in the aspect of mitochondrial dysfunction may be used as therapeutic targets in obese-asthma. In asthma, the infiltrated inflammatory cells increase 12/15-LOX which secretes linoleic acid metabolite (13-S-HODE) which causes mitochondrial dysfunction by activating TRPV1 that disturbs calcium homeostasis and increases mitochondrial calcium overload to cause mitochondrial dysfunction. On the other hand, inflammation leads to increase in the expressions of arginase and iNOS which consume L-arginine to cause less bioavailability of L-arginine to eNOS. Further, increased ADMA uncouples eNOS to generate more ROS and peroxynitrite which cause mitochondrial dysfunction. The resultant mitochondrial dysfunction in airway epithelia leads to injure airway epithelia and causes airway hyperresponsiveness. Most of the sequences of increased free fatty acid in metabolic syndrome have been explained in Figure 1. Thus, 12/15-LOX inhibition, improving ER health, TRPV1 inhibition, increased eNOS, and mitochondrial nutrients could be possible therapeutic targets in obese-asthmatic condition. TRPV1: transient receptor potential cation channel, subfamily V, member 1; ONOO⁻: peroxynitrite.