You’re probably tired of me proclaiming magic bullets for the cure of obesity which is still pretty intractable. But one day one of these magic bullets is going to be the one. I need to do a list of all the magic bullets so far but before that there’s yet another to talk about.
There is this recently discovered enzyme called nicotinamide N-methyltransferase (NNMT) that is very abundant and busy in white adipose tissue and serves as a critical regulator of the energy metabolism of cells. It has been found that blocking this enzyme causes weight loss and fixes lots of the rest of the story that happens when you are obese. These guys at the University of Texas Medical Branch At Galveston, Texas have reported (1) of some of their work with NNMT. Here they treated diet induced obesity in mice with a molecule called 5-amino-1-methylquinolium that blocks the business of NNMT. They found that it was truly a (the?) magic bullet, causing weight loss, mostly fat loss, and fixing things like fatty liver disease (non-alcoholic fatty liver disease (NASH)). They concluded, “Collectively, NNMT’s master regulatory involvement in key metabolic processes in the metabolically active tissues (adipose, liver, and muscle) suggests that NNMT may represent an attractive, druggable target serving as a niche access point to treat obesity and related chronic metabolic diseases.”
Ok so that’s it in a nutshell. But in wading through the many pages of this paper I can make some observations that may just be idiosyncratic to me. One thing about mice is you can make them fat with a high fat diet. Then once they made their mouse subjects fat they fed them diets called lean diet and “Western diet.” This seems like a social requirement in deference to the usual wrong presumptions about obesity. The lean diet by itself caused a little weight loss and was fed to both the treated and the control mice. When first switched to the lean diet the mice ate less for awhile until I guess they got used to it and then they all ate the same number of calories. Seems like you could just feed them all regular mouse chow and skip the hassle of all the other rigmarole.
There were some intriguing intersections with the methionine story of my last article that are complicated and that I don’t understand very well.
Also the lead author of this report is the founder of the company that made the NNMT inhibitor used to experiment on these mice. I need to find out if I can buy stock in that company or at least get on the payroll as the janitor if they have a stock option benefit.
1. Sampson, C.M., Dimet, A.L., Neelakantan, H. et al. Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice. Sci Rep 11, 5637 (2021). https://doi.org/10.1038/s41598-021-85051-6
This writer’s opinion is their own and not the opinion of this newspaper
John DiTraglia M.D. is a Pediatrician in Portsmouth. He can be reached by e-mail- firstname.lastname@example.org or phone-354-6605.