Nitrite treatment rescues cardiac dysfunction in aged mice treated with conjugated linoleic acid

Abstract

Conjugated linoleic acid (cLA) is a commercially available weight loss supplement that is not currently regulated by the FDA. Numerous studies suggest that cLA mediates protection in diseases including cancer, diabetes, atherosclerosis, immune function, and obesity. Based upon these reports, it was hypothesized that supplementation of cLA would improve heart function in aged wild-type (WT) mice. At 10 months of age, mice were treated with cLA, nitrite, or the combination of the two. Echocardiograms revealed that cardiac function was decreased in aged compared to young WT mice, as determined by percent of fractional shortening (%FS). Also, contrary to the hypothesis, mice that received cLA (6-week treatment) had significantly worse cardiac function compared to controls. This effect was attenuated when mice were co-treated with cLA and nitrite. Taken together, these results suggest that cLA-mediated cardiac injury can be circumvented following nitrite supplementation in a murine model of aging.

Co-treatment with conjugated linoleic acid and nitrite modulates mitochondrial respiration and electron transport chain activity in vivo and attenuates mitochondrial dysfunction during cardiac injury.

“…Interestingly, nitrite supplemenation in aged mice treated with cLA was able to rescue cardiac left ventricular dysfunction (107). This was mediated by restoring eNOS dimerization and NO signaling.…”

“…cLA has been shown to increase ROS in macrophages (105), oxidative stress in rat cardiac tissue (106), and 8-iso-prostaglandin F2α urine levels in obese males (104). cLA has also been shown to induce cardiac dysfunction in aging by uncoupled eNOS (107). These results suggest that cLA may exacerbate oxidative stress conditions such as MI, aging and obesity.…”

“…However, the hydrogen peroxide was measured in cardiac tissue homogenate thereby the source of hydrogen peroxide could differ between the nitrite treatment and co-treatment as nitrite can increase NADH oxidase 2 (NOX2), a mediator of non-mitochondrial ROS generation (107).…”

“…This was mediated by restoring eNOS dimerization and NO signaling. These results coupled with nitrite being unable to rescue aged mitochondrial function, suggest the more prominent role of nitrite in aging is to restore NO signaling which is lost within the vasculature during aging (107,147).…”

“…Due to the high abundance of the cis-9 trans-11 isomer of cLA within the diet it is important to study the isomeric specific effects. The cis-9 trans-11 isomer of cLA decreased cardiac function in aged mice and co-administration of nitrite reversed this cardiac dysfunction (107). The interaction of cLA and nitrite brings up an overlooked mechanism of action of cLA; the nitration of cLA.…”