Nicotinamide induces male-specific body weight loss in the postnatal period through molecular regulation of the hypothalamus and liver

Molecular mechanisms of body weight control have been discovered recently and much research focuses on the hypothalamic regulation of food intake and the hepatic regulation of glucose utility. We previously reported that postnatal nicotinamide treatment reduced brain dopamine and body weight. To further investigate the differential effects of nicotinamide-mediated body weight loss, nicotinamide (i.p. 100 mg/kg) was injected into postnatal and adult mice twice a week for 4 weeks. Interestingly, following nicotinamide treatment, male postnatal mice displayed reduced body weight and spontaneous motor activity. No significant changes were observed in adult and postnatal female mice or adult male mice following nicotinamide treatment. In male postnatal mice, hypothalamic agouti-related peptide (AGRP) and proopiomelanocortin (POMC) levels were increased in the arcuate nucleus following nicotinamide treatment. Neuropeptide Y (NPY) levels were unchanged in both male and female mice. Additionally, nicotinamide-injected male postnatal mice had increased glucose 6-phosphatase (G6Pase) and decreased phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. These results indicate that hypothalamic POMC and hepatic PEPCK are important molecules that mediate nicotinamide-induced weight loss in postnatal male mice.

► Nicotinamide reduced male-specific body weight and locomotor activity in the postnatal period but not in the adult period.
► Hypothalamic POMC and AGRP were increased following nicotinamide injection in postnatal males.
► Hepatic G6Pase and PEPCK showed the opposite patterns of expression in the postnatal mouse from nicotinamide.