Nicotinamide N-methyltransferase inhibition in diet-induced obesity

Summary

This study evaluated the metabolic effects of nicotinamide N-methyltransferase (NNMT) inhibition using 5-amino-1-methylquinolinium (5-amino-1MQ) in a diet-induced obesity mouse model. Systemic treatment with the NNMT inhibitor reduced body weight, decreased adipocyte size, and improved metabolic parameters by increasing intracellular NAD+ and SAM levels in white adipose tissue.

Key Findings

• 5-amino-1MQ treatment (20 mg/kg/day) reduced body weight by approximately 7% over 11 days in diet-induced obese mice without affecting food intake
• NNMT inhibition decreased white adipose tissue mass and reduced mean adipocyte size, indicating enhanced lipid mobilization
• Treatment increased intracellular NAD+ and S-adenosylmethionine (SAM) levels in adipose tissue, restoring the methylation and energy metabolism pathways suppressed by NNMT overexpression in obesity