VitB3 3D model
It will allow for novel drug development for obesity, diabetes type II and related metabolic diseases. A small molecule N1-methylnicotinamide prevents metabolic complications caused by a high-fat diet.
“Our laboratory investigates the metabolic effects of nicotinamide adenine dinucleotide [NAD+], a metabolite derived from a form of vitamin B3 called nicotinamide,” explained assistant Prof Pavlos Pissios. NAD+ is central to intermediary metabolism, the intracellular process by which food is converted into cellular components in the body.
“Like reservatrol, which is found in red wine, NAD+ boosts the effects of the protein sirtuin 1 [Sirt1], which is known to provide many health benefits,” said Pissios. “Interest in the metabolic effects of NAD+ has spurred the production of several new dietary supplements to improve metabolic health and delay aging. While these results have yet to be demonstrated in humans, recent research has shown that boosting tissue levels of NAD+ can improve health and reduce metabolic complications in mice that have been fed a high-fat diet.”
They showed nicotinamide N-methyltransfersase (NNMT), a “clearance” enzyme that helps the body excrete excess vitamin B3, also plays a more prominent metabolic role. It has now found to be also involved in the regulation of liver metabolism. N1-methylnicotinamide, the product of nicotinamide methylation by NNMT, increases Sirt1 protein levels and improves metabolism.”
SIRT1
In subsequent experiments, Pissios and colleagues found that NNMT correlated positively with Sirt1 and a healthy metabolic profile in mice, and also showed that humans with low cholesterol and low triglycerides exhibited high levels of NNMT and Sirt1 in their livers.
“Since N1-methylnicotinamide is a small molecule, we were able to feed it directly to mice to find out if it would prevent the metabolic complications caused by a high-fat diet,” said Pissios. As predicted, N1-methylnicotinamide increased liver Sirt1 protein and suppressed triglyceride and cholesterol synthesis resulting in a healthier liver—with fewer inflammatory markers, less liver fat and lower cholesterol compared to control groups.
“We have now identified a new vitamin B3 pathway that regulates liver metabolism and provides us with an opportunity to pursue development of novel treatments for metabolic diseases,” said Pissios.
http://www.eurekalert.org/pub_releases/2015-08/bidm-bri080615.php
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