Obesity after neonatal overfeeding is independent of hypothalamic microgliosis

J Neuroendocrinol. 2019 Aug;31(8):e12757. doi: 10.1111/jne.12757. Epub 2019 Jul 15.

Abstract

The early-life environment is important in programming brain development, and metabolic disruptions at this time can have long-lasting effects. Previously, we have shown that rats overfed for the first 3 weeks of their neonatal life maintain obesity into adulthood. Neonatal overfeeding also leads to primed hypothalamic and hippocampal microglia that are hyper-responsive to an immune challenge in adulthood. However, whether this microglial priming contributes to the obese phenotype and whether it is possible to reverse either the obesity or the microglial priming are not clear. In the present study, we hypothesised that an intervention with minocycline during the juvenile period (postnatal day 21-42) would normalise both the microglial priming and obesity. To induce obesity in neonatal Wistar rats, we manipulated the litter sizes in which they were suckled, yielding litters of 12 (control-fed) or four (neonatally overfed). After weaning, we administered minocycline i.p. every second day for a 3-week period and examined body composition and microglial profiles 24 hours following an immune challenge with lipopolysaccharide. As demonstrated previously, neonatal overfeeding resulted in prolonged weight gain. However, minocycline failed to reverse this effect. Minocycline did reverse microglial priming in feeding-related regions of the hypothalamus, with minimal effects on pro-inflammatory cytokines and on microglial number and morphology in the hippocampus. Thus, the programming effect of neonatal overfeeding on microglial priming can be ameliorated by minocycline later in life. However, the persistent obesity seen after neonatal overfeeding is likely not driven by changes in hypothalamic inflammation and microglial activity.

Keywords: hippocampus; hypothalamus; microglia; neonate; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cellular Reprogramming / drug effects
  • Encephalitis / complications
  • Encephalitis / pathology
  • Encephalitis / physiopathology*
  • Female
  • Hypothalamus / drug effects
  • Hypothalamus / pathology*
  • Male
  • Microglia / drug effects
  • Microglia / pathology
  • Microglia / physiology*
  • Minocycline / pharmacology
  • Obesity / etiology*
  • Obesity / pathology
  • Obesity / physiopathology
  • Overnutrition / complications*
  • Overnutrition / pathology
  • Overnutrition / physiopathology
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Weight Gain / drug effects
  • Weight Gain / physiology

Substances

  • Minocycline