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EASD: Effects of Nitric Oxide on Insulin Clearance and Hepatic Lipid Metabolism

Higher levels of hypothalamic nitric oxide could lead to less insulin clearance and more lipogenesis….

Nitric oxide (NO) is an important neurotransmitter produced in the paraventricular nucleus (PVN) of the hypothalamus. Previous studies suggested that the level of NO was inversely correlated with systemic insulin clearance. However, little is known about the metabolic consequences of PVN NO-mediated regulation of insulin clearance.

In a recent study posted online in the 2014 European Association for the Study of Diabetes (EASD) Virtual Meeting, Dr. Fatima Martins from the Universidade Nova de Lisboa and colleagues assessed the metabolic consequences of PVN NO in male Wistar rats. These rats underwent brain surgery for nucleus specific infusion in the PVN region. Rats in the treatment group received a bolus dose of 250ug/2uL of L-NAME, while rats in the control group received 2uL of saline solution in each side of the brain.

Researchers observed that PVN NO depletion resulted in changes in insulin signaling as well as glucose and lipid metabolism. Expression of IRS-1 and AKT genes were increasing, while expression of hepatic Glut 1, 2 and 4 were all decreased significantly, suggesting a decrease in glucose uptake by the liver.

The depletion of PVN NO also suppressed lipogenic enzymes (ACC, FAS, ATP citrate lyase and pATP citrate lyase), resulting in the diminishing of hepatic non-sterified fatty acids (NEFA) content. However, hepatic triglyceride levels and expression of hepatic DGAT gene were increased, possibly in response to decreased NEFA.

“These results support the hypothesis that increased PVN NO results in a decreased insulin clearance and a stimulation of de novo lipogenesis. This suggests that hypothalamic NO signaling has a role in regulating hepatic lipid metabolism,” concluded the researchers.

Practice Pearls:

  • NO is most likely to involve in the insulin signaling and hepatic lipid metabolism.
  • Results from this study suggested that increased PVN NO could lead to less insulin clearance and more lipogenesis.
  • Future studies should be conducted to assess the metabolic consequences of NO in human.

Martins F, Tovar S, Jones J. Hypothalamic nitric oxide regulates insulin signaling and hepatic lipid metabolism. EASD Virtual Meeting. Web. 25 Sep 2014.