| First Author | Tenopoulou M | Year | 2018 |
| Journal | JCI Insight | Volume | 3 |
| Issue | 16 | PubMed ID | 30135317 |
| Mgi Jnum | J:288048 | Mgi Id | MGI:6407488 |
| Doi | 10.1172/jci.insight.122156 | Citation | Tenopoulou M, et al. (2018) Oral nitrite restores age-dependent phenotypes in eNOS-null mice. JCI Insight 3(16) |
| abstractText | Alterations in the synthesis and bioavailability of NO are central to the pathogenesis of cardiovascular and metabolic disorders. Although endothelial NO synthase-derived (eNOS-derived) NO affects mitochondrial long-chain fatty acid beta-oxidation, the pathophysiological significance of this regulation remains unclear. Accordingly, we determined the contributions of eNOS/NO signaling in the adaptive metabolic responses to fasting and in age-induced metabolic dysfunction. Four-month-old eNOS-/- mice are glucose intolerant and exhibit serum dyslipidemia and decreased capacity to oxidize fatty acids. However, during fasting, eNOS-/- mice redirect acetyl-CoA to ketogenesis to elevate circulating levels of beta-hydroxybutyrate similar to wild-type mice. Treatment of 4-month-old eNOS-/- mice with nitrite for 10 days corrected the hypertension and serum hyperlipidemia and normalized the rate of fatty acid oxidation. Fourteen-month-old eNOS-/- mice exhibited metabolic derangements, resulting in reduced utilization of fat to generate energy, lower resting metabolic activity, and diminished physical activity. Seven-month administration of nitrite to eNOS-/- mice reversed the age-dependent metabolic derangements and restored physical activity. While the eNOS/NO signaling is not essential for the metabolic adaptation to fasting, it is critical for regulating systemic metabolic homeostasis in aging. The development of age-dependent metabolic disorder is prevented by low-dose replenishment of bioactive NO. |
