Neonatal leptin antagonism improves metabolic programming of postnatally overnourished mice.

Abstract

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.

• Authors: Gustav Colldén, Emilie Caron, Sebastien G Bouret
• Journal: International journal of obesity (2005) (Int J Obes (Lond)) Vol. 46 Issue 6 Pg. 1138-1144 (06 2022) ISSN: 1476-5497 [Electronic] England
• PMID: 35173277 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Leptin

Topics

• Animals
• Female
• Hypothalamus (metabolism)
• Leptin (metabolism)
• Mice
• Obesity (metabolism)
• Overnutrition (metabolism)
• Pregnancy
• Weight Gain