Neonatal leptin antagonism improves metabolic programming of postnatally overnourished mice

Int J Obes (Lond). 2022 Jun;46(6):1138-1144. doi: 10.1038/s41366-022-01093-4. Epub 2022 Feb 16.


Background/objectives: Alteration of the perinatal nutritional environment is an important risk factor for the development of metabolic diseases in later life. The hormone leptin plays a critical role in growth and development. Previous studies reported that postnatal overnutrition increases leptin secretion during the pre-weaning period. However, a direct link between leptin, neonatal overnutrition, and lifelong metabolic regulation has not been investigated.

Methods: We used the small litter mouse model combined with neonatal leptin antagonist injections to examine whether attenuating leptin during early life improves lifelong metabolic regulation in postnatally overnourished mice.

Results: Postnatally overnourished mice displayed rapid weight gain during lactation and remained overweight as adults. These mice also showed increased adiposity and perturbations in glucose homeostasis in adulthood. Neonatal administration of a leptin antagonist normalized fat mass and insulin sensitivity in postnatally overnourished mice. These metabolic improvements were associated with enhanced sensitivity of hypothalamic neurons to leptin.

Conclusions: Early postnatal overnutrition causes metabolic alterations that can be permanently attenuated with the administration of a leptin antagonist during a restricted developmental window.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Hypothalamus / metabolism
  • Leptin* / metabolism
  • Mice
  • Obesity / metabolism
  • Overnutrition* / metabolism
  • Pregnancy
  • Weight Gain


  • Leptin