5-Amino-1MQ · UK research stock

NNMT methylates nicotinamide, a precursor of NAD+, using S-adenosylmethionine (SAM) as the methyl donor. Interest in blocking it began with a 2014 study in which knocking NNMT down in the fat and liver of mice protected them against diet-induced obesity by raising energy expenditure, with higher SAM and NAD+ in adipose tissue ^[3]. In cultured adipocytes, 5-amino-1MQ lowered the enzyme's product, 1-methylnicotinamide, raised intracellular NAD+ and SAM and suppressed lipogenesis, without inhibiting the related methyltransferases and NAD+ salvage enzymes it was tested against ^[2]. In diet-induced obese mice, an 11-day course reduced body weight and white fat mass and lowered plasma cholesterol, with no change in food intake ^[2].

Later work from the same group extends this to diet and ageing. Combined with a switch to a lean diet, it improved fat loss and liver fat in obese mice beyond the diet alone ^[4]. In mice aged 22 to 24 months, eight weeks of treatment was associated with about 40% greater grip strength in sedentary animals, an effect that added to that of exercise ^[5].